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1
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Abdull Rahim U, Mustapa M, Mohamed Shakrin NNS, Nurdin A, Mohamad Taridi N, Yusof YAM, Mad Nordin MF, Che Roos NA. Current evidence and future direction on evaluating the anticancer effects of curcumin, gingerols, and shogaols in cervical cancer: A systematic review. PLoS One 2024; 19:e0314280. [PMID: 39576841 PMCID: PMC11584093 DOI: 10.1371/journal.pone.0314280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 11/06/2024] [Indexed: 11/24/2024] Open
Abstract
Cervical cancer ranked fourth most common malignancy among women worldwide despite the establishment of vaccination programmes. This systematic review evaluates the anti-cancer properties of turmeric and ginger bioactive compounds, specifically curcumin, 6/10-gingerol, and 6/10-shogaol, and their combination in cervical cancer through in-vitro and in-vivo models. A comprehensive electronic search was performed using Science Direct, PubMed, and Scopus from inception until the second week of June 2024 for studies published in English. Only studies investigating the effects of curcumin, gingerol, shogaol, and/or their combination in human cervical cancer cell lines and/or rodent animal models implanted with cervical cancer xenografts were included. Altogether, 27 studies were included in this review. The evidence gathered indicated that curcumin, 6/10-gingerol and 6-shogaol exert their anticancer action through modulation of cell signalling pathways, including AMPK, WNT, PI3K/AKT, and NF-κB pathway, and mediators including Bax/Bcl2, TNF-α, EGFR, COX-2, caspases-3, -9, p53, and pRb. However, the synergistic effect of these bioactive compounds is not known due to lack of evidence. In conclusion, curcumin, 6/10-gingerols, and 6-shogaols hold promise as therapeutic agents for cervical cancer. Yet, further research is essential to understand their combined efficacy, emphasising the need for additional studies exploring the synergistic anticancer effects of these bioactive compounds. Additional factors to explore include long-term effects and susceptibility of chemoresistant cervical cancer cells towards curcumin, shogaols, and gingerols.
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Affiliation(s)
- Unwaniah Abdull Rahim
- Biochemistry Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
| | - Marami Mustapa
- Anatomy Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
| | - Nik Noorul Shakira Mohamed Shakrin
- Centre for Tropicalization (CENTROP), National Defence University of Malaysia, Kuala Lumpur, Malaysia
- Medical Microbiology and Immunology Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
| | - Armania Nurdin
- Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
- Laboratory of UPM-MAKNA Cancer Research (CANRES), Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | - Nursiati Mohamad Taridi
- Biochemistry Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
| | - Yasmin Anum Mohd Yusof
- Biochemistry Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
| | - Mariam Firdhaus Mad Nordin
- Malaysia-Japan International Institute of Technology, UTM Kuala Lumpur, Jalan Sultan Yahya Petra, Kuala Lumpur, Malaysia
| | - Nur Aishah Che Roos
- Pharmacology Unit, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia
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2
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Veselá K, Kejík Z, Masařík M, Babula P, Dytrych P, Martásek P, Jakubek M. Curcumin: A Potential Weapon in the Prevention and Treatment of Head and Neck Cancer. ACS Pharmacol Transl Sci 2024; 7:3394-3418. [PMID: 39539276 PMCID: PMC11555516 DOI: 10.1021/acsptsci.4c00518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 09/27/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024]
Abstract
Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent. Numerous studies have shown that curcumin and its derivatives have the potential to affect signaling pathways (NF-κB, JAK/STAT, and EGFR) and molecular mechanisms that are crucial for the growth and migration of head and neck tumors. Furthermore, its ability to interact with the tumor microenvironment and trigger the immune system may significantly influence the organism's immune response to the tumor. Combining curcumin with conventional therapies such as chemotherapy or radiotherapy may improve the efficacy of treatment and reduce the side effects of treatment, thereby increasing its therapeutic potential. This review is a comprehensive overview that discusses both the benefits and limitations of curcumin and its therapeutic effects in the context of tumor biology, with an emphasis on molecular mechanisms in the context of HNC. This review also includes possibilities to improve the limiting properties of curcumin both in terms of the development of new derivatives, formulations, or combinations with conventional therapies that have potential as a new type of therapy for the treatment of HNC and subsequent use in clinical practice.
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Affiliation(s)
- Kateřina Veselá
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Zdeněk Kejík
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Michal Masařík
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
- Department
of Physiology, Faculty of Medicine, Masaryk
University, Kamenice 5, 625 00 Brno, Czech Republic
- Department
of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Petr Babula
- Department
of Physiology, Faculty of Medicine, Masaryk
University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Petr Dytrych
- First
Department of Surgery-Department of Abdominal, Thoracic Surgery and
Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 121
08 Prague, Czech
Republic
| | - Pavel Martásek
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Milan Jakubek
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
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3
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Arslan I. Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy. Nat Prod Res 2024; 38:3644-3656. [PMID: 37690001 DOI: 10.1080/14786419.2023.2254454] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/20/2023] [Accepted: 08/28/2023] [Indexed: 09/11/2023]
Abstract
One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal actin assembly, phenotypic signalling, and transcription process which affects a wide range of cellular processes such as cell motility, invasion, metastasis, cell growth, angiogenesis, and cell cycle progression. Most recently, PAK1 was shown to be involved in the progression of coronavirus-caused pulmonary inflammation (lung fibrosis), but clinical data is not currently available yet. This review highlights the naturally occurring compounds that inhibit the oncogenic, melanogenic, and ageing kinase PAK1. Additionally, the potent anti-inflammatory effects of natural products in an attempt to prevent pulmonary fibrosis in COVID-19 have also been discussed.
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Affiliation(s)
- Idris Arslan
- Zonguldak Bülent Ecevit University, Faculty of Science, Molecular Biology and Genetics, Zonguldak, Turkey
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4
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Yang Y, Du Y, Cui B. Polyphenols targeting multiple molecular targets and pathways for the treatment of vitiligo. Front Immunol 2024; 15:1387329. [PMID: 39119340 PMCID: PMC11306171 DOI: 10.3389/fimmu.2024.1387329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 07/11/2024] [Indexed: 08/10/2024] Open
Abstract
Vitiligo, a pigmentary autoimmune disorder, is marked by the selective loss of melanocytes in the skin, leading to the appearance of depigmented patches. The principal pathological mechanism is the melanocyte destruction mediated by CD8+ T cells, modulated by oxidative stress and immune dysregulation. Vitiligo affects both physical health and psychological well-being, diminishing the quality of life. Polyphenols, naturally occurring compounds with diverse pharmacological properties, including antioxidant and anti-inflammatory activities, have demonstrated efficacy in managing various dermatological conditions through multiple pathways. This review provides a comprehensive analysis of vitiligo and the therapeutic potential of natural polyphenolic compounds. We examine the roles of various polyphenols in vitiligo management through antioxidant and immunomodulatory effects, melanogenesis promotion, and apoptosis reduction. The review underscores the need for further investigation into the precise molecular mechanisms of these compounds in vitiligo treatment and the exploration of their combination with current therapies to augment therapeutic outcomes.
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Affiliation(s)
| | | | - Bingnan Cui
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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5
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Islam MR, Rauf A, Akash S, Trisha SI, Nasim AH, Akter M, Dhar PS, Ogaly HA, Hemeg HA, Wilairatana P, Thiruvengadam M. Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives. Biomed Pharmacother 2024; 170:116034. [PMID: 38141282 DOI: 10.1016/j.biopha.2023.116034] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 12/08/2023] [Accepted: 12/14/2023] [Indexed: 12/25/2023] Open
Abstract
The curry powder spices turmeric (Curcuma longa L.), which contains curcumin (diferuloylmethane), an orange-yellow chemical. Polyphenols are the most commonly used sources of curcumin. It combats oxidative stress and inflammation in diseases, such as hyperlipidemia, metabolic syndrome, arthritis, and depression. Most of these benefits are due to their anti-inflammatory and antioxidant properties. Curcumin consumption leads to decreased bioavailability, resulting in limited absorption, quick metabolism, and quick excretion, which hinders health improvement. Numerous factors can increase its bioavailability. Piperine enhances bioavailability when combined with curcumin in a complex. When combined with other enhancing agents, curcumin has a wide spectrum of health benefits. This review evaluates the therapeutic potential of curcumin with a specific emphasis on its approach based on molecular signaling pathways. This study investigated its influence on the progression of cancer, inflammation, and many health-related mechanisms, such as cell proliferation, apoptosis, and metastasis. Curcumin has a significant potential for the prevention and treatment of various diseases. Curcumin modulates several biochemical pathways and targets involved in cancer growth. Despite its limited tissue accumulation and bioavailability when administered orally, curcumin has proven useful. This review provides an in-depth analysis of curcumin's therapeutic applications, its molecular signaling pathway-based approach, and its potential for precision medicine in cancer and human health.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Akash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Sadiya Islam Trisha
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Akram Hossain Nasim
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Muniya Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Puja Sutro Dhar
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Hanan A Ogaly
- Chemistry Department, College of Science, King Khalid University, Abha 61421, Saudi Arabia
| | - Hassan A Hemeg
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Taibah University, Al-Medinah Al-Monawara, Saudi Arabia
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
| | - Muthu Thiruvengadam
- Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 05029, Republic of Korea; Department of Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India.
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6
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Abualhasan M, Jaradat N, Hawash M, Shraim N, Asaad M, Mousa A, Mousa Z, Tobeh R, Mlitat B. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine. Open Life Sci 2023; 18:20220767. [PMID: 38027225 PMCID: PMC10668110 DOI: 10.1515/biol-2022-0767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/02/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Curcuma longa (turmeric) is a plant that has been extensively utilized in traditional medicine for centuries. Turmeric has a long history of use in both food and traditional medicine for the treatment of ailments such as diarrhea, cancer, flatulence, and dyspepsia. In Palestine, this plant was cultivated for the first time. The objective of this study was to characterize the extract of C. longa and assess its antimutagenic activity against a variety of cancer cells. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) methods were employed to identify the constituents of turmeric. The cytotoxic effects of C. longa were evaluated on cancer and normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. The results revealed the presence of 10 components in turmeric extract as identified by GC-MS. The major constituents comprising 78% of the total constituents were α-zingiberene (27.51%), tumeron (19.44%), β-sesquiphellandrene (19.40%), and aromatic-tumeron (11.63%). HPLC analysis successfully separated the main constituent, curcumin (1.78%), along with two other curcumin derivatives. The cytotoxicity results demonstrated potent anticancer activity of the C. longa extract against HeLa and LX2 cell lines, with IC50 values of 46.84 ± 2.12 and 29.77 ± 1 µg/mL, respectively. Furthermore, the plant extract at a concentration of 250 µg/mL exhibited over 95% inhibition against all tested cancer cell lines. These findings highlight the promising potential of turmeric as a natural source with powerful anticancer activities. Moreover, the extract may possess other biological activities such as antioxidant and antimicrobial properties, which could be explored in future studies.
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Affiliation(s)
- Murad Abualhasan
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Nidal Jaradat
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Mohammed Hawash
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Naser Shraim
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Mohammad Asaad
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Ahmed Mousa
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Zain Mousa
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Reem Tobeh
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Balsam Mlitat
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
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7
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Kaur Sandhu S, Raut J, Kumar S, Singh M, Ahmed B, Singh J, Rana V, Rishi P, Ganesh N, Dua K, Pal Kaur I. Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing. Int J Pharm 2023; 643:123187. [PMID: 37394156 DOI: 10.1016/j.ijpharm.2023.123187] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 06/25/2023] [Accepted: 06/26/2023] [Indexed: 07/04/2023]
Abstract
Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-β, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.
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Affiliation(s)
- Simarjot Kaur Sandhu
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Jayant Raut
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Suneel Kumar
- Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08844, USA
| | - Mandeep Singh
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Bakr Ahmed
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Joga Singh
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Vikas Rana
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India
| | - Praveen Rishi
- Department of Microbiology, Panjab University, Chandigarh 160014, India
| | - Narayanan Ganesh
- Jawaharlal Nehru Cancer Hospital & Research Centre, Bhopal 462001, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, New South Wales 2007, Australia
| | - Indu Pal Kaur
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
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8
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Huang SL, Chang TC, Sun NK. Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity. Biochem Pharmacol 2023; 212:115581. [PMID: 37146834 DOI: 10.1016/j.bcp.2023.115581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/24/2023] [Accepted: 04/26/2023] [Indexed: 05/07/2023]
Abstract
The therapeutic activity of paclitaxel against ovarian carcinoma is relatively low due to the frequent occurrence of chemoresistance and disease recurrence. We found earlier that a combination of curcumin and paclitaxel reduces cell viability and promotes apoptosis in paclitaxel-resistant (i.e., taxol-resistant, Txr) ovarian cancer cells. In the present study, we first used RNA sequencing (RNAseq) analysis to identify genes that are upregulated in Txr cell lines but downregulated by curcumin in ovarian cancer cells. The nuclear factor kappa B (NFκB) signaling pathway was shown to be upregulated in Txr cells. Furthermore, based on the protein interaction database BioGRID, we found that Smad nuclear interacting protein 1 (SNIP1) may be involved in regulating the activity of NFκB in Txr cells. Accordingly, curcumin upregulated SNIP1 expression, which in turn downregulated the pro-survival genes Bcl-2 and Mcl-1. Using shRNA-guided gene silencing, we found that SNIP1 depletion reversed the inhibitory effect of curcumin on NFκB activity. Moreover, we identified that SNIP1 enhanced NFκB protein degradation, thereby suppressing NFκB/p65 acetylation, which is involved in the inhibitory effect of curcumin on NFκB signaling. The transcription factor early growth response protein 1 (EGR1) was shown to represent an upstream transactivator of SNIP1. Consequently, we show that curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells.
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Affiliation(s)
- Shang-Lang Huang
- Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China
| | - Ting-Chang Chang
- Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan, Republic of China
| | - Nian-Kang Sun
- Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan, Republic of China.
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9
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Sitthirach C, Charoensuk L, Pairojkul C, Chaidee A, Intuyod K, Pongking T, Thongpon P, Jantawong C, Hongsrichan N, Waraasawapati S, Yingklang M, Pinlaor S. Curcumin-loaded nanocomplexes ameliorate the severity of nonalcoholic steatohepatitis in hamsters infected with Opisthorchis viverrini. PLoS One 2022; 17:e0275273. [PMID: 36166461 PMCID: PMC9514634 DOI: 10.1371/journal.pone.0275273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 09/13/2022] [Indexed: 11/18/2022] Open
Abstract
Background
Comorbidity of Opisthorchis viverrini (OV) infection and nonalcoholic fatty-liver disease (NAFLD) enhances NAFLD progression to nonalcoholic steatohepatitis (NASH) by promoting severe liver inflammation and fibrosis. Here, we investigated the effect of supplementation with curcumin-loaded nanocomplexes (CNCs) on the severity of NASH in hamsters.
Methodology
Hamsters were placed in experimental groups as follows: fed standard chow diet (normal control, NC); fed only high-fat and high-fructose (HFF) diet; O. viverrini-infected and fed HFF diet (HFFOV); group fed with blank nanocomplexes (HFFOV+BNCs); groups fed different doses of CNCs (25, 50 and 100 mg/kg body weight: HFFOV+CNCs25; HFFOV+CNCs50; HFFOV+CNCs100, respectively) and a group given native curcumin (HFFOV+CUR). All treatment were for three months.
Results
The HFF group revealed NAFLD as evidenced by hepatic fat accumulation, ballooning, mild inflammation and little or no fibrosis. These changes were more obvious in the HFFOV group, indicating development of NASH. In contrast, in the HFFOV+CNCs50 group, histopathological features indicated that hepatic fat accumulation, cell ballooning, cell inflammation and fibrosis were lower than in other treatment groups. Relevantly, the expression of lipid-uptake genes, including fatty-acid uptake (cluster of differentiation 36), was reduced, which was associated with the lowering of alanine aminotransferase, total cholesterol and triglyceride (TG) levels. Reduced expression of an inflammation marker (high-mobility group box protein 1) and a fibrosis marker (alpha smooth-muscle actin) were also observed in the HFFOV+CNCs50 group.
Conclusion
CNCs treatment attenuates the severity of NASH by decreasing hepatic steatosis, inflammation, and fibrosis as well as TG synthesis. CNCs mitigate the severity of NASH in this preclinical study, which indicates promise for future use in patients.
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Affiliation(s)
- Chutima Sitthirach
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Lakhanawan Charoensuk
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Chawalit Pairojkul
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Apisit Chaidee
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Kitti Intuyod
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Thatsanapong Pongking
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand
| | - Phonpilas Thongpon
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Chanakan Jantawong
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Medical Technology, Faculty of Allied Health Science, Nakhonratchasima College, Nakhon Ratchasima, Thailand
| | - Nuttanan Hongsrichan
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Sakda Waraasawapati
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Manachai Yingklang
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Department of Fundamentals of Public Health, Faculty of Public Health, Burapha University, Chonburi, Thailand
| | - Somchai Pinlaor
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- * E-mail:
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10
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Rahman MM, Sarker MT, Alam Tumpa MA, Yamin M, Islam T, Park MN, Islam MR, Rauf A, Sharma R, Cavalu S, Kim B. Exploring the recent trends in perturbing the cellular signaling pathways in cancer by natural products. Front Pharmacol 2022; 13:950109. [PMID: 36160435 PMCID: PMC9498834 DOI: 10.3389/fphar.2022.950109] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/15/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer is commonly thought to be the product of irregular cell division. According to the World Health Organization (WHO), cancer is the major cause of death globally. Nature offers an abundant supply of bioactive compounds with high therapeutic efficacy. Anticancer effects have been studied in a variety of phytochemicals found in nature. When Food and Drug Administration (FDA)-approved anticancer drugs are combined with natural compounds, the effectiveness improves. Several agents have already progressed to clinical trials based on these promising results of natural compounds against various cancer forms. Natural compounds prevent cancer cell proliferation, development, and metastasis by inducing cell cycle arrest, activating intrinsic and extrinsic apoptosis pathways, generating reactive oxygen species (ROS), and down-regulating activated signaling pathways. These natural chemicals are known to affect numerous important cellular signaling pathways, such as NF-B, MAPK, Wnt, Notch, Akt, p53, AR, ER, and many others, to cause cell death signals and induce apoptosis in pre-cancerous or cancer cells without harming normal cells. As a result, non-toxic “natural drugs” taken from nature’s bounty could be effective for the prevention of tumor progression and/or therapy of human malignancies, either alone or in combination with conventional treatments. Natural compounds have also been shown in preclinical studies to improve the sensitivity of resistant cancers to currently available chemotherapy agents. To summarize, preclinical and clinical findings against cancer indicate that natural-sourced compounds have promising anticancer efficacy. The vital purpose of these studies is to target cellular signaling pathways in cancer by natural compounds.
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Affiliation(s)
- Md. Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Taslim Sarker
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Mst. Afroza Alam Tumpa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Yamin
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Tamanna Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, Pakistan
- *Correspondence: Abdur Rauf, ; Bonglee Kim,
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
- *Correspondence: Abdur Rauf, ; Bonglee Kim,
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11
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Fetoni AR, Paciello F, Troiani D. Cisplatin Chemotherapy and Cochlear Damage: Otoprotective and Chemosensitization Properties of Polyphenols. Antioxid Redox Signal 2022; 36:1229-1245. [PMID: 34731023 DOI: 10.1089/ars.2021.0183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Significance: Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including redox imbalance caused by reactive oxygen species production and lipid peroxidation, activation of inflammation, and p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies to reduce side effect toxicities while preserving or enhancing the antineoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, that is, normal cells undergoing stressful conditions versus cancer cells. Critical Issues: This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/cross talk between the cell's defenses, inflammatory molecules, and the key signaling molecules of signal transducers and activators of transcription 3 (STAT-3), nuclear factor κ-B (NF-κB), p53, and nuclear factor erythroid 2-related factor 2 (Nrf-2). Future Directions: We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols. Antioxid. Redox Signal. 36, 1229-1245.
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Affiliation(s)
- Anna Rita Fetoni
- Department of Head and Neck Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Fabiola Paciello
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Diana Troiani
- Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy
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12
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Koroth J, Mahadeva R, Ravindran F, Parashar TR, Teja V, Karki SS, Choudhary B. Curcumin derivative 1, 2-bis [(3E, 5E)-3, 5-bis [(2-chlorophenyl) methylene]-4-oxo-1-piperidyl] ethane-1, 2-dione (ST03) induces mitochondria mediated apoptosis in ovarian cancer cells and inhibits tumor progression in EAC mouse model. Transl Oncol 2022; 15:101280. [PMID: 34801859 PMCID: PMC8607274 DOI: 10.1016/j.tranon.2021.101280] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 01/02/2023] Open
Abstract
Curcumin is known for its anticancer properties, but its clinical application is limited due to its poor bioavailability and chemical stability. In this study we report the curcumin derivative, ST03 (1,2-bis[(3E,5E)-3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidyl]ethane-1,2-dione) exhibits ∼ 14 fold better bioavailability compared to curcumin and is detectable in plasma up to 12 h. ST03 induces ROS, activates the intrinsic apoptotic pathway as evident by disruption of mitochondrial membrane potential, and induction of proapoptotic proteins in ovarian cancer lines PA1 and A2780. ST03 also blocked the migration of ovarian cancer cells. ST03 exerted its antitumor effect in-vivo in the EAC mouse model by activating the intrinsic apoptotic pathway. Our findings demonstrate ST03, a curcumin derivative, with better bioavailability and stability with no discernable toxicity in vivo to be a promising drug candidate for anticancer therapies.
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Affiliation(s)
- Jinsha Koroth
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India; Manipal Academy of Higher Education, Manipal 576104, India
| | - Raghunandan Mahadeva
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India
| | - Febina Ravindran
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India
| | - Tanvi R Parashar
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India
| | - Vinay Teja
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India
| | - Subhas S Karki
- Department of Pharmaceutical Chemistry, KLE Academy of Higher Education and Research, KLE College of Pharmacy, Rajajinagar, Bangalore, KN, India
| | - Bibha Choudhary
- Institute of Bioinformatics and Applied Biotechnology, Electronic city phase 1, Bangalore 560100, Karnataka, India.
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13
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Begum D, Merchant N, Nagaraju GP. Role of selected phytochemicals on gynecological cancers. A THERANOSTIC AND PRECISION MEDICINE APPROACH FOR FEMALE-SPECIFIC CANCERS 2021:1-30. [DOI: 10.1016/b978-0-12-822009-2.00001-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Tiwari A, Jain SK. Curcumin Based Drug Delivery Systems for Cancer Therapy. Curr Pharm Des 2020; 26:5430-5440. [DOI: 10.2174/1381612826666200429095503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/22/2020] [Indexed: 01/04/2023]
Abstract
Cancer accounts for the second major cause of death globally. Conventional cancer therapies lead to
systemic toxicity that forbids their long term application. Besides, tumor resistance and recurrence have been
observed in the majority of cases. Thus, the development of such therapy, which will pose minimum side effects,
is the need of the hour. Curcumin or diferuloylmethane (CUR) is a natural polyphenol bioactive (obtained from
Curcuma longa) which possesses anti-cancer and chemo-preventive activity. It acts by modulating various components
of signaling cascades that are involved in cancer cell proliferation, invasion, and apoptosis process. It
interacts with the adaptive and innate immune systems of our body and causes tumor regression. This may be the
reason behind the attainment of in vivo anti-tumor activity at a very low concentration. Its ease of availability,
safety profile, low cost, and multifaceted role in cancer prevention and treatment has made it a promising agent
for chemoprevention of many cancers. Regardless of the phenomenal properties, its clinical utility is haltered due
to its low aqueous solubility, poor bioavailability, rapid metabolism, and low cellular uptake. In the last few
years, a variety of novel drug carriers have been fabricated to enhance the bioavailability and pharmacokinetic
profile of CUR to attain better targeting of cancer. In this review, the recent developments in the arena of nanoformulations,
like liposomes, polymeric NPs, solid lipid NPs (SNPs), polymeric micelles, nanoemulsions, microspheres,
nanogels, etc. in anticancer therapy have been discussed along with a brief overview of the molecular
targets for CUR in cancer therapy and role of CUR in cancer immunotherapy.
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Affiliation(s)
- Ankita Tiwari
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.), 470 003, India
| | - Sanjay K. Jain
- Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.), 470 003, India
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15
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Kianamiri S, Dinari A, Sadeghizadeh M, Rezaei M, Daraei B, Bahsoun NEH, Nomani A. Mitochondria-Targeted Polyamidoamine Dendrimer-Curcumin Construct for Hepatocellular Cancer Treatment. Mol Pharm 2020; 17:4483-4498. [PMID: 33205974 DOI: 10.1021/acs.molpharmaceut.0c00566] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Mitochondrial malfunction plays a crucial role in cancer development and progression. Cancer cells show a substantially higher mitochondrial activity and greater mitochondrial transmembrane potential than normal cells. This concept can be exploited for targeting cytotoxic drugs to the mitochondria of cancer cells using mitochondrial-targeting compounds. In this study, a polyamidoamine dendrimer-based mitochondrial delivery system was prepared for curcumin using triphenylphosphonium ligands to improve the anticancer efficacy of the drug in vitro and in vivo. For the in vitro evaluations, various methods, such as viability assay, confocal microscopy, flow cytometry, reactive oxygen species (ROS), and real-time polymerase chain reaction analyses, were applied. Our findings showed that the targeted-dendrimeric curcumin (TDC) could successfully deliver and colocalize the drug to the mitochondria of the cancer cells, and selectively induce a potent apoptosis and cell cycle arrest at G2/M. Moreover, at a low curcumin dose of less than 25 μM, TDC significantly reduced adenosine triphosphate and glutathione, and increased the ROS level of the isolated rat hepatocyte mitochondria. The in vivo studies on the Hepa1-6 tumor-bearing mice also indicated a significant tumor suppression effect and the highest median survival days (Kaplan-Meier survival estimation and log-rank test) after treatment with the TDC construct compared to the free curcumin and untargeted construct. Besides its targeted nature and safety, the expected improved solubility and stability represent the prepared targeted-dendrimeric construct as an up-and-coming candidate for cancer treatment. The results of this study emphasize the promising route of mitochondrial targeting as a practical approach for cancer therapy, which can be achieved by optimizing the delivery method.
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Affiliation(s)
- Shahla Kianamiri
- Department of Nano-Biotechnology, School of Biological Science, Tarbiat Modares University, Tehran 14115-175, Iran
| | - Ali Dinari
- Department of Nano-Biotechnology, School of Biological Science, Tarbiat Modares University, Tehran 14115-175, Iran
| | - Majid Sadeghizadeh
- Department of Nano-Biotechnology, School of Biological Science, Tarbiat Modares University, Tehran 14115-175, Iran.,Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran 14115-175, Iran
| | - Mohsen Rezaei
- Department of Toxicology, School of Medical Sciences, Tarbiat Modares University, Tehran 14115-111, Iran
| | - Bahram Daraei
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 14155-6153, Iran
| | - Noor El-Huda Bahsoun
- Department of Chemical Engineering, University of Waterloo, Waterloo ON N2L 3G1, Canada
| | - Alireza Nomani
- Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan 45139-56184, Iran
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16
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Verapamil Inhibits Mitochondria-Induced Reactive Oxygen Species and Dependent Apoptosis Pathways in Cerebral Transient Global Ischemia/Reperfusion. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5872645. [PMID: 33133347 PMCID: PMC7591985 DOI: 10.1155/2020/5872645] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022]
Abstract
The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.
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17
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Perera WPTD, Dissanayake RK, Ranatunga UI, Hettiarachchi NM, Perera KDC, Unagolla JM, De Silva RT, Pahalagedara LR. Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications. RSC Adv 2020; 10:30785-30795. [PMID: 35516060 PMCID: PMC9056367 DOI: 10.1039/d0ra05755j] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 08/12/2020] [Indexed: 12/25/2022] Open
Abstract
Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP-Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO-curcumin nanoparticles (SZNP-Cs) and rod-shaped ZnO-curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP-Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.
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Affiliation(s)
- W P T D Perera
- Academy of the Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
| | - Ranga K Dissanayake
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
- Department of Pharmacy and Pharmaceutical Sciences, Faculty of Allied Health Sciences, University of Sri Jayewardenepura Gangodawila Nugegoda 10250 Sri Lanka
| | - U I Ranatunga
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo 25 Kynsey Road Colombo 00800 Sri Lanka
| | - N M Hettiarachchi
- Academy of the Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
| | - K D C Perera
- Academy of the Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
| | - Janitha M Unagolla
- Biomedical Engineering Program, Department of Bioengineering, College of Engineering, University of Toledo Toledo OH 43607 USA
| | - R T De Silva
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
| | - L R Pahalagedara
- Sri Lanka Institute of Nanotechnology, Nanotechnology and Science Park Mahenwatte, Pitipana Homagama 10206 Sri Lanka
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18
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Surapally S, Jayaprakasam M, Verma RS. Curcumin augments therapeutic efficacy of TRAIL-based immunotoxins in leukemia. Pharmacol Rep 2020; 72:1032-1046. [PMID: 32141025 DOI: 10.1007/s43440-020-00073-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/26/2019] [Accepted: 12/30/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) has been perceived as a promising anti-cancer agent because of its unique ability to kill cancer cells while sparing normal cells. However, translation of TRAIL to clinical studies was less successful as a large number of cancer cells acquire resistance to TRAIL-based monotherapies. An ideal strategy to overcome TRAIL resistance is to combine it with potential sensitizing agents. OBJECTIVE To investigate the TRAIL-sensitizing effect of curcumin in leukemia. METHODS The mechanism underlying TRAIL sensitization by curcumin was studied by flow cytometric analysis of TRAIL receptors in leukemic cell lines and patient samples, and immunoblot detection of TRAIL-apoptosis signaling proteins. RESULTS Curcumin augments TRAIL-apoptotic signaling in leukemic cells by upregulating the expression of DR4 and DR5 along with suppression of cFLIP and anti-apoptotic proteins Mcl-1, Bcl-xl, and XIAP. Curcumin pre-treatment significantly (p < 0.01) enhanced the sensitivity of leukemic cell lines to TRAIL recombinant proteins. IL2-TRAIL peptide in the presence of curcumin induced potent apoptosis (p < 0.001) as compared to TRAIL and IL2-TRAIL protein in leukemic cell lines with IC50 < 0.1 μΜ. Additionally, the combination of IL2-TRAIL peptide and curcumin showed significant cytotoxicity in patient peripheral blood mononuclear cells (PBMCs) with an efficacy of 90% in acute myeloid leukemia (AML), but 100% in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML). CONCLUSION Overall, our results suggest that curcumin potentiates TRAIL-induced apoptosis through modulation of death receptors and anti-apoptotic proteins which significantly enhances the therapeutic efficacy.
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Affiliation(s)
- Sridevi Surapally
- Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India
| | - Madhumathi Jayaprakasam
- Division of Epidemiology and Communicable Diseases, Indian Council for Medical Research (ICMR), New Delhi, India
| | - Rama Shanker Verma
- Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Building, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India.
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19
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Abd. Wahab NA, H. Lajis N, Abas F, Othman I, Naidu R. Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer. Nutrients 2020; 12:E679. [PMID: 32131560 PMCID: PMC7146610 DOI: 10.3390/nu12030679] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/22/2020] [Accepted: 02/26/2020] [Indexed: 12/22/2022] Open
Abstract
Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
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Affiliation(s)
- Nurul Azwa Abd. Wahab
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
| | - Nordin H. Lajis
- Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia; (N.H.L.); (F.A.)
| | - Faridah Abas
- Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia; (N.H.L.); (F.A.)
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia
| | - Iekhsan Othman
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
| | - Rakesh Naidu
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; (N.A.A.W.); (I.O.)
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20
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Adachi S, Hamoya T, Fujii G, Narita T, Komiya M, Miyamoto S, Kurokawa Y, Takahashi M, Takayama T, Ishikawa H, Tashiro K, Mutoh M. Theracurmin inhibits intestinal polyp development in Apc-mutant mice by inhibiting inflammation-related factors. Cancer Sci 2020; 111:1367-1374. [PMID: 31991021 PMCID: PMC7156816 DOI: 10.1111/cas.14329] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 01/18/2020] [Accepted: 01/21/2020] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well‐known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc‐mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10‐20 µM Theracurmin for 24 hours reduced nuclear factor‐κB (NF‐κB) transcriptional activity in human colon cancer DLD‐1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF‐κB promoter transcriptional activity. As NF‐κB is a regulator of inflammation‐related factors, we next investigated the downstream targets of NF‐κB: monocyte chemoattractant protein‐1 (MCP‐1) and interleukin (IL)‐6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP‐1 and IL‐6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J‐CAP‐C study).
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Affiliation(s)
- Saeko Adachi
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.,Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushuu University, Fukuoka, Japan
| | - Takahiro Hamoya
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Gen Fujii
- Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan
| | - Takumi Narita
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Masami Komiya
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Shingo Miyamoto
- Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan
| | - Yurie Kurokawa
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Maiko Takahashi
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Faculty of Medicine Graduate School of Medical Sciences, University of Tokushima, Tokushima, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kosuke Tashiro
- Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushuu University, Fukuoka, Japan
| | - Michihiro Mutoh
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.,Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan
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21
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Ma Y, Wang Q, Wang D, Huang J, Sun R, Mao X, Tian Y, Xia Q. Silica-Lipid Hybrid Microparticles as Efficient Vehicles
for Enhanced Stability and Bioaccessibility of Curcumin. Food Technol Biotechnol 2019; 57:319-330. [PMID: 31866745 PMCID: PMC6902299 DOI: 10.17113/ftb.57.03.19.6035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Curcumin is an active ingredient with multiple functions, but its application is often restricted due to its poor water solubility, weak stability, and consequently low bioaccessibility. Based on this, the aim of this work is to develop a new vehicle to overcome these restrictions. Here we developed a curcumin-loaded nanoemulsion and then curcumin-loaded silica-lipid hybrid microparticles through emulsification and vacuum drying, respectively. The loading of curcumin in the nanoemulsion and microparticles was (0.30±0.02) and (0.67±0.02) %, respectively. FTIR and XRD analyses of microparticles revealed that curcumin was encapsulated in porous, amorphous silica. In vitro antioxidant activities showed that the encapsulation would not affect the antioxidant activity of curcumin. In vitro simulated digestion indicated that nanoemulsion and microparticles had higher curcumin bioaccessibility than the control group. The storage stability of microparticles remained the same during 6 weeks in the dark at 4, 25 and 40 °C. Moreover, the microparticles had a better chemical stability than nanoemulsion under the light. The cell viability was over 80% when the concentration of nanocarriers was less than 45 μg/mL. Hence, the microparticles could be a promising means to load curcumin and improve its solubility, light stability and bioaccessibility.
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Affiliation(s)
- Yudi Ma
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China.,Collaborative Innovation Center of Suzhou Nano Science and Technology, No. 150 Renai Road 215123 Suzhou, PR China
| | - Qiang Wang
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China.,Collaborative Innovation Center of Suzhou Nano Science and Technology, No. 150 Renai Road 215123 Suzhou, PR China
| | - Dantong Wang
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China.,Collaborative Innovation Center of Suzhou Nano Science and Technology, No. 150 Renai Road 215123 Suzhou, PR China
| | - Juan Huang
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China.,Collaborative Innovation Center of Suzhou Nano Science and Technology, No. 150 Renai Road 215123 Suzhou, PR China
| | - Rui Sun
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China
| | - Xinyu Mao
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China
| | - Yuan Tian
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China
| | - Qiang Xia
- School of Biological Science and Medical Engineering, State Key Laboratory of Bioelectronics, Southeast University, No.2, Sipailou Street, 210096 Nanjing, PR China.,National Demonstration Center for Experimental Biomedical Engineering Education, Southeast University, No. 2, Sipailou Street, 210096 Nanjing,
PR China.,Collaborative Innovation Center of Suzhou Nano Science and Technology, No. 150 Renai Road 215123 Suzhou, PR China
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22
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Mechanistic Evaluation of Enhanced Curcumin Delivery through Human Skin In Vitro from Optimised Nanoemulsion Formulations Fabricated with Different Penetration Enhancers. Pharmaceutics 2019; 11:pharmaceutics11120639. [PMID: 31805660 PMCID: PMC6956259 DOI: 10.3390/pharmaceutics11120639] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 11/24/2019] [Accepted: 11/25/2019] [Indexed: 01/01/2023] Open
Abstract
Curcumin is a natural product with chemopreventive and other properties that are potentially useful in treating skin diseases, including psoriasis and melanoma. However, because of the excellent barrier function of the stratum corneum and the relatively high lipophilicity of curcumin (log P 3.6), skin delivery of curcumin is challenging. We used the principles of a Quality by Design (QbD) approach to develop nanoemulsion formulations containing biocompatible components, including Labrasol and Lecithin as surfactants and Transcutol and ethanol as cosurfactants, to enhance the skin delivery of curcumin. The nanoemulsions were characterised by cryo-SEM, Zeta potential, droplet size, pH, electrical conductivity (EC) and viscosity (η). Physicochemical long-term stability (6 months) was also investigated. The mean droplet sizes as determined by dynamic light scattering (DLS) were in the lower submicron range (20–50 nm) and the average Zeta potential values were low (range: −0.12 to −2.98 mV). Newtonian flow was suggested for the nanoemulsions investigated, with dynamic viscosity of the nanoemulsion formulations ranging from 5.8 to 31 cP. The droplet size of curcumin loaded formulations remained largely constant over a 6-month storage period. The inclusion of terpenes to further enhance skin permeation was also examined. All nanoemulsions significantly enhanced the permeation of curcumin through heat-separated human epidermal membranes, with the greatest effect being a 28-fold increase in maximum flux (Jmax) achieved with a limonene-based nanoemulsion, compared to a 60% ethanol in water control vehicle. The increases in curcumin flux were associated with increased skin diffusivity. In summary, we demonstrated the effectiveness of nanoemulsions for the skin delivery of the lipophilic active compound curcumin, and elucidated the mechanism of permeation enhancement. These formulations show promise as delivery vehicles for curcumin to target psoriasis and skin cancer, and more broadly for other skin delivery applications.
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23
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Li Q, Xing S, Chen Y, Liao Q, Li Q, Liu Y, He S, Feng F, Chen Y, Zhang J, Liu W, Guo Q, Sun Y, Sun H. Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases. Eur J Med Chem 2019; 185:111862. [PMID: 31735576 DOI: 10.1016/j.ejmech.2019.111862] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 11/06/2019] [Accepted: 11/06/2019] [Indexed: 02/06/2023]
Abstract
Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases.
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Affiliation(s)
- Qi Li
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Shuaishuai Xing
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Ying Chen
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Qinghong Liao
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Qihang Li
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Yang Liu
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Siyu He
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Feng Feng
- Jiangsu Food and Pharmaceutical Science College, No.4 Meicheng Road, Huai'an, 223003, PR China
| | - Yao Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, PR China
| | - Jie Zhang
- Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Wenyuan Liu
- Department of Analytical Chemistry, School of Pharmacy, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, PR China
| | - Qinglong Guo
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China
| | - Yuan Sun
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, 95817, USA
| | - Haopeng Sun
- Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China; Jiangsu Food and Pharmaceutical Science College, No.4 Meicheng Road, Huai'an, 223003, PR China.
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24
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Mahalunkar S, Yadav AS, Gorain M, Pawar V, Braathen R, Weiss S, Bogen B, Gosavi SW, Kundu GC. Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer. Int J Nanomedicine 2019; 14:8285-8302. [PMID: 31802866 PMCID: PMC6801194 DOI: 10.2147/ijn.s215142] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 07/27/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. METHODS We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. RESULTS Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. CONCLUSION These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.
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Affiliation(s)
- Sneha Mahalunkar
- School of Basic Medical Science, Savitribai Phule Pune University, Pune411007, Maharashtra, India
| | - Amit Singh Yadav
- Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune411007, India
| | - Mahadeo Gorain
- Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune411007, India
| | - Vinay Pawar
- Institute of Immunology, Hannover Medical School, Hannover, Germany
- Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Ranveig Braathen
- K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Oslo University Hospital, Oslo0027, Norway
| | - Siegfried Weiss
- Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - Bjarne Bogen
- K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Oslo University Hospital, Oslo0027, Norway
| | - Suresh W Gosavi
- Department of Physics, Savitribai Phule Pune University, Pune411007, Maharashtra, India
| | - Gopal C Kundu
- Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune411007, India
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25
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Fahmy HM. In vitro study of the cytotoxicity of thymoquinone/curcumin fluorescent liposomes. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:1465-1476. [PMID: 31377882 DOI: 10.1007/s00210-019-01688-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 06/28/2019] [Indexed: 01/14/2023]
Abstract
In the present study, thymoquinone-loaded liposomes (Lip (TQ)), curcumin-encapsulated liposome (Lip (CUR)), and thymoquinone/curcumin-encapsulated liposome (Lip (TQ + CUR)) in addition to rhodamine-labeled thymoquinone/curcumin liposome (Lip (TQ + CUR + ROD)) were prepared with encapsulation efficiency exceeding 99%. The aim of the present study was to evaluate the effect of the different prepared formulations either labeled with the fluorescent dye (rhodamine B) or not on A549 lung cancer cells. Cytotoxicity of different formulations was assessed by MTT assay. Proliferation of A549 cells was significantly inhibited by the different formulations in a concentration-dependent manner in 72 h. The Lip (TQ + CUR + ROD) formulation demonstrated the lowest IC50 value. To investigate its mechanism of action on A549 lung cancer cells, the Comet assay (for DNA damage) was done, the measurement of some oxidative stress parameters in addition to performing inverted fluorescence microscopy imaging. The results of the present study demonstrated the increased DNA damage, oxidative stress damage, and cell apoptosis in A549 treated with TQ, CUR, and rhodamine-encapsulated fluorescent liposome formulation as compared to untreated cells. The results obtained from the present study demonstrate the significant role of the TQ/CUR fluorescent liposomes on decreasing the viability of A549 lung cancer cells. Graphical abstract.
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Affiliation(s)
- Heba Mohamed Fahmy
- Biophysics Department, Faculty of Science, Cairo University, 16 El Zafer Street, Haram, Giza, Egypt.
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26
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Vallée A, Lecarpentier Y, Vallée JN. Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway. J Exp Clin Cancer Res 2019; 38:323. [PMID: 31331376 PMCID: PMC6647277 DOI: 10.1186/s13046-019-1320-y] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 07/10/2019] [Indexed: 12/13/2022] Open
Abstract
Numerous studies have presented that curcumin could have a positive effect in the prevention of cancer and then in tumor therapy. Several hypotheses have highlighted that curcumin could decreases tumor growth and invasion by acting on both chronic inflammation and oxidative stress. This review focuses on the interest of use curcumin in cancer therapy by acting on the WNT/β-catenin pathway to repress chronic inflammation and oxidative stress. In the cancer process, one of the major signaling pathways involved is the WNT/β-catenin pathway, which appears to be upregulated. Curcumin administration participates to the downregulation of the WNT/β-catenin pathway and thus, through this action, in tumor growth control. Curcumin act as PPARγ agonists. The WNT/β-catenin pathway and PPARγ act in an opposed manner. Chronic inflammation, oxidative stress and circadian clock disruption are common and co-substantial pathological processes accompanying and promoting cancers. Circadian clock disruption related to the upregulation of the WNT/β-catenin pathway is involved in cancers. By stimulating PPARγ expression, curcumin can control circadian clocks through the regulation of many key circadian genes. The administration of curcumin in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/β-catenin pathway and PPARγ activity levels.
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Affiliation(s)
- Alexandre Vallée
- Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Hotel-Dieu Hospital, AP-HP, Université Paris Descartes, 1 place du Parvis de Notre-Dame, Paris, France
| | - Yves Lecarpentier
- Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien (GHEF), 6-8 rue Saint-fiacre, 77100 Meaux, France
| | - Jean-Noël Vallée
- Centre Hospitalier Universitaire (CHU) Amiens Picardie, Université Picardie Jules Verne (UPJV), 80054 Amiens, France
- Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France
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27
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Bessone F, Argenziano M, Grillo G, Ferrara B, Pizzimenti S, Barrera G, Cravotto G, Guiot C, Stura I, Cavalli R, Dianzani C. Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells. NANOTECHNOLOGY 2019; 30:214004. [PMID: 30654342 DOI: 10.1088/1361-6528/aaff96] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.
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Affiliation(s)
- F Bessone
- Department of Drug Science & Technology, University of Torino, Torino, Italy
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28
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Bahrami A, Majeed M, Sahebkar A. Curcumin: a potent agent to reverse epithelial-to-mesenchymal transition. Cell Oncol (Dordr) 2019; 42:405-421. [PMID: 30980365 DOI: 10.1007/s13402-019-00442-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Epithelial-to-mesenchymal transition (EMT) is involved in tumor progression, invasion, migration and metastasis. EMT is a process by which polarized epithelial cells acquire motile mesothelial phenotypic features. This process is initiated by disassembly of cell-cell contacts through the loss of epithelial markers and replacement of these markers by mesenchymal markers. Reconstruction of the cytoskeleton and degradation of the tumor basement membrane ensures the spread of invasive malignant tumor cells to distant locations. Accumulating evidence indicates that curcumin, as a well-known phytochemical, can inhibit EMT/metastasis through various mechanisms and pathways in human tumors. CONCLUSIONS In this review, we summarize the mechanisms by which curcumin may affect EMT in cells under pathological conditions to understand its potential as a novel anti-tumor agent. Curcumin can exert chemo-preventive effects by inhibition and reversal of the EMT process through both TGF-β-dependent (e.g. in hepatoma and retinal pigment epithelial cancer) and -independent (e.g. in oral cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma, breast cancer, melanoma, prostate cancer, bladder cancer, thyroid cancer and lung cancer) pathways. Curcumin can also mitigate chemoresistance through EMT suppression and promotion of the antiproliferative effects of conventional chemotherapeutics. Therefore, curcumin has the potential to be used as a novel adjunctive agent to prevent tumor metastasis, which may at least partly be attributed to its hampering of the EMT process.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Amirhossein Sahebkar
- Department of Medical Biotechnology Research Center, School of Medicine, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, P.O. Box: 91779-48564, Mashhad, Iran.
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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29
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Rao PS, Ramanjaneyulu YS, Prisk VR, Schurgers LJ. A Combination of Tamarindus indica seeds and Curcuma longa Rhizome Extracts Improves Knee Joint Function and Alleviates Pain in Non-Arthritic Adults Following Physical Activity. Int J Med Sci 2019; 16:845-853. [PMID: 31337958 PMCID: PMC6643110 DOI: 10.7150/ijms.32505] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Accepted: 04/11/2019] [Indexed: 11/05/2022] Open
Abstract
Background: Knee joint pain is the most common reason for physical disability which associates with age. TamaFlexTM (NXT15906F6) is a synergistic anti-inflammatory formulation which contains ethanol/aqueous extracts of Tamarindus indica seeds and ethanol extract of Curcuma longa rhizome. Methods: In a 90-day randomized, double-blind, placebo-controlled study, we evaluated efficacy of NXT15906F6 in relieving pain and improving joint function in non-arthritic adults. Ninety non-arthritic subjects who experienced knee pain and joint discomfort following a six-minute walk test (SMWT) and Stair climb test (SCT) participated in the present trial. Subjects received either 250 mg (n=30) or 400 mg (n=30) of NXT15906F6 or matched placebo (PL: n=30) daily for 90 days. Improvement from baseline six-minute walk distance (SMWD) in NXT15906F6 groups, compared with placebo (PL) was the primary outcome of the study. Results: At post-intervention, subjects in NXT15906F6-250 (p<0.001) and NXT15906F6-400 (p<0.0001) groups showed substantial improvements in mean changes of SMWD from baseline compared to placebo. The 250 mg and 400 mg NXT15906F6 groups also improved average walking speed from baseline by 0.08±0.07 m/s (p=0.0010) and 0.11±0.08 m/s (p<0.0001), respectively. The NXT15906F6 groups experienced significant improvement in SMWT performances as early as 14 days. NXT15906F6-supplemented participants showed a consistent benefit of pain relief and improved musculoskeletal functions, compared to placebo. Conclusion: NXT15906F6 provided substantial relief from knee pain after physical activity and improved joint function in non-arthritic adults. Study participants did not show any major adverse events, and they tolerated well this novel herbal formulation.
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Affiliation(s)
| | | | | | - Leon J Schurgers
- Department of Biochemistry, Maastricht University, Maastricht, The Netherlands
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30
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Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability. Drug Deliv Transl Res 2018; 8:1389-1405. [PMID: 29845380 DOI: 10.1007/s13346-018-0543-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.
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31
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Coker-Gurkan A, Bulut D, Genc R, Arisan ED, Obakan-Yerlikaya P, Palavan-Unsal N. Curcumin prevented human autocrine growth hormone (GH) signaling mediated NF-κB activation and miR-183-96-182 cluster stimulated epithelial mesenchymal transition in T47D breast cancer cells. Mol Biol Rep 2018; 46:355-369. [PMID: 30467667 DOI: 10.1007/s11033-018-4479-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 11/07/2018] [Indexed: 12/13/2022]
Abstract
Autocrine growth hormone (GH) signaling is a promoting factor for breast cancer via triggering abnormal cell growth, proliferation, and metastasis, drug resistance. Curcumin (diferuloylmethane), a polyphenol derived from turmeric (Curcuma longa), has anti-proliferative, anti-carcinogenic, anti-hormonal effect via acting on PI3K/Akt, NF-κB and JAK/STAT signaling. Forced GH expression induced epithelial mesenchymal transition (EMT) through stimulation of miR-182-96-183 cluster expression in breast cancer cells. This study aimed to investigate the role of NF-κB signaling and miR-182-96-183 cluster expression profile on autocrine GH-mediated curcumin resistance, which was prevented by time-dependent curcumin treatment in T47D breast cancer cells. Dose- and time-dependent effect of curcumin on T47D wt and GH+ breast cancer cells were evaluated by MTT cell viability and trypan blue assay. Apoptotic effect of curcumin was determined by PI and Annexin V/PI FACS flow analysis. Immunoblotting performed to investigate the effect of curcumin on PI3K/Akt/MAPK, NF-κB signaling. miR182-96-183 cluster expression profile was observed by qRT-PCR. Overexpression of GH triggered resistant profile against curcumin (20 µM) treatment for 24 h, but this resistance was accomplished following 48 h curcumin exposure. Concomitantly, forced GH induced invasion and metastasis through EMT and NF-κB activation were prevented by long-term curcumin exposure in T47D cells. Moreover, 48 h curcumin treatment prevented the autocrine GH-mediated miR-182-96-183 cluster expression stimulation in T47D cells. In consequence, curcumin treatment for 48 h, prevented autocrine GH-triggered invasion-metastasis, EMT activation through inhibiting NF-κB signaling and miR-182-96-183 cluster expression and induced apoptotic cell death by modulating Bcl-2 family members in T47D breast cancer cells.
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Affiliation(s)
- Ajda Coker-Gurkan
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey.
| | - Derya Bulut
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey
| | - Recep Genc
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey
| | - Elif-Damla Arisan
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey
| | - Pınar Obakan-Yerlikaya
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey
| | - Narcin Palavan-Unsal
- Molecular Biology and Genetics Department, Science and Letters Faculty, Istanbul Kultur University, Atakoy Campus, 34156, Istanbul, Turkey
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Carolina Alves R, Perosa Fernandes R, Fonseca-Santos B, Damiani Victorelli F, Chorilli M. A Critical Review of the Properties and Analytical Methods for the Determination of Curcumin in Biological and Pharmaceutical Matrices. Crit Rev Anal Chem 2018; 49:138-149. [PMID: 30252504 DOI: 10.1080/10408347.2018.1489216] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Curcumin, a natural compound extracted from turmeric (Curcuma longa), has been extensively studied because of its various pharmacological properties, such as anti-inflammatory, antioxidant, antibiotic, antiprotozoal, immunomodulatory, anti-proliferative, antitumor, and anticarcinogenic effects. However, low solubility in aqueous media has limited its therapeutic applications. To overcome these bioavailability issues, the use of drug delivery systems providing localized or targeted delivery of this drug may represent a more viable therapeutic option. Several drug delivery systems have been shown to significantly enhance the therapeutic efficacy of curcumin. Additionally, a wide variety of analytical methods are available for the qualitative and quantitative analysis of curcumin in different matrices, including plant extracts, biological fluids, and drug delivery systems. There are a variety of methodologies to quantify curcumin, but chromatographic and spectroscopic techniques are the ones most commonly used. Thus, in this review, we evaluate the biological properties of curcumin, as well as its nanotechnology-based delivery systems and methods of analysis.
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Affiliation(s)
- Renata Carolina Alves
- a School of Pharmaceutical Sciences , São Paulo State University (UNESP) , Araraquara, São Paulo , Brazil
| | | | - Bruno Fonseca-Santos
- a School of Pharmaceutical Sciences , São Paulo State University (UNESP) , Araraquara, São Paulo , Brazil
| | | | - Marlus Chorilli
- a School of Pharmaceutical Sciences , São Paulo State University (UNESP) , Araraquara, São Paulo , Brazil
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Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. Int J Pharm 2018; 550:333-346. [PMID: 30179702 DOI: 10.1016/j.ijpharm.2018.08.060] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 08/21/2018] [Accepted: 08/31/2018] [Indexed: 02/04/2023]
Abstract
The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI < 0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/mL) and FRAP (1.19 ± 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.
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Cheng YY, Hsieh CH, Tsai TH. Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics. J Food Drug Anal 2018; 26:S88-S95. [PMID: 29703390 PMCID: PMC9326883 DOI: 10.1016/j.jfda.2018.01.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 01/13/2018] [Accepted: 01/20/2018] [Indexed: 02/06/2023] Open
Abstract
With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. Therefore, this study aimed to collect the results of pharmacokinetic studies relating to the concurrent use of cancer chemotherapy and complementary and alternative therapies. According to the National Health Insurance (NHI) database in Taiwan and several publications, the three most commonly prescribed formulations for cancer patients are Xiang-Sha-Liu-Jun-Zi-Tang, Jia-Wei-Xiao-Yao-San and Bu-Zhong-Yi-Qi-Tang. The three most commonly prescribed single herbs for cancer patients are Hedyotis diffusa, Scutellaria barbata, and Astragalus membranaceus. Few studies have discussed herb-drug interactions involving these herbs from a pharmacokinetics perspective. Here, we reviewed Jia-Wei-Xiao-Yao-San, Long-Dan-Xie-Gan-Tang, Curcuma longa and milk thistle to provide information based on pharmacokinetic evidence for healthcare professionals to use in educating patients about the risks of the concomitant use of various remedies.
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Affiliation(s)
- Yung-Yi Cheng
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, 112, Taiwan
| | - Chen-Hsi Hsieh
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, 112, Taiwan; Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, National Yang-Ming University, Taipei, 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, 404, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; Department of Chemical Engineering, National United University, Miaoli, 36063, Taiwan.
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Cavaleri F. Presenting a New Standard Drug Model for Turmeric and Its Prized Extract, Curcumin. Int J Inflam 2018; 2018:5023429. [PMID: 29568482 PMCID: PMC5820622 DOI: 10.1155/2018/5023429] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 12/06/2017] [Indexed: 02/07/2023] Open
Abstract
Various parts of the turmeric plant have been used as medicinal treatment for various conditions from ulcers and arthritis to cardiovascular disease and neuroinflammation. The rhizome's curcumin extract is the most studied active constituent, which exhibits an expansive polypharmacology with influence on many key inflammatory markers. Despite the expansive reports of curcucmin's therapeutic value, clinical reliability and research repeatability with curcumin treatment are still poor. The pharmacology must be better understood and reliably mapped if curcumin is to be accepted and used in modern medical applications. Although the polypharmacology of this extract has been considered, in mainstream medicine, to be a drawback, a perspective change reveals a comprehensive and even synergistic shaping of the NF-kB pathway, including transactivation. Much of the inconsistent research data and unreliable clinical outcomes may be due to a lack of standardization which also pervades research standard samples. The possibility of other well-known curcumin by-products contributing in the polypharmacology is also discussed. A new flowchart of crosstalk in transduction pathways that lead to shaping of nuclear NF-kB transactivation is generated and a new calibration or standardization protocol for the extract is proposed which could lead to more consistent data extraction and improved reliability in therapy.
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Affiliation(s)
- Franco Cavaleri
- Biologic Pharmamedical Research, 688-2397 King George Blvd., White Rock, BC, Canada V4A7E9
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Krishnamoorthy A, Tavoosi N, Chan GKL, Liu J, Ren G, Cavigiolio G, Ryan RO. Effect of curcumin on amyloid-like aggregates generated from methionine-oxidized apolipoprotein A-I. FEBS Open Bio 2018; 8:302-310. [PMID: 29435420 PMCID: PMC5794470 DOI: 10.1002/2211-5463.12372] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 12/06/2017] [Accepted: 12/12/2017] [Indexed: 12/13/2022] Open
Abstract
Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. In this study, we investigated the anti‐amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A‐I was strongly quenched. At the same time, curcumin fluorescence emission was enhanced. The fluorescence emission spectra of curcumin in the presence of amyloid‐like aggregates formed by methionine‐oxidized (ox) apoA‐I varied, depending on whether curcumin was added before, or after, aggregate formation. The impact of curcumin on the structure of the aggregating material was revealed by the lower amount of β‐structure in ox‐apoA‐I amyloid‐like aggregates formed in the presence of curcumin, compared to aggregates formed without curcumin. However, the kinetics of ox‐apoA‐I amyloid‐like aggregate formation was not altered by the presence of curcumin. Moreover, electron microscopy analysis detected no discernable differences in amyloid morphology when ox‐apoA‐I amyloid‐like aggregates were formed in the presence or absence of curcumin. In conclusion, curcumin interacts with apoA‐I and alters the structure of ox‐apoA‐I amyloid‐like aggregates yet does not diminish the propensity of ox‐apoA‐I to form aggregates.
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Affiliation(s)
- Aparna Krishnamoorthy
- Department of Nutritional Sciences and Toxicology University of California Berkeley CA USA
| | - Narjes Tavoosi
- Children's Hospital Oakland Research Institute CA USA.,Present address: Department of Biotechnology College of Science University of Tehran Iran
| | - Gary K L Chan
- Children's Hospital Oakland Research Institute CA USA
| | - Jianfang Liu
- Lawrence Berkeley National Laboratory The Molecular Foundry Berkeley CA USA
| | - Gang Ren
- Lawrence Berkeley National Laboratory The Molecular Foundry Berkeley CA USA
| | | | - Robert O Ryan
- Department of Nutritional Sciences and Toxicology University of California Berkeley CA USA.,Children's Hospital Oakland Research Institute CA USA.,Department of Biochemistry and Molecular Biology University of Nevada Reno NV USA
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Rajkumari S, Sanatombi K. Nutritional value, phytochemical composition, and biological activities of edible Curcuma species: A review. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2018. [DOI: 10.1080/10942912.2017.1387556] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
| | - K. Sanatombi
- Department of Biotechnology, Manipur University, Imphal, India
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38
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Mohammadi S, Kayedpoor P, Karimzadeh-Bardei L, Nabiuni M. The Effect of Curcumin on TNF-α, IL-6 and CRP Expression in a Model of Polycystic Ovary Syndrome as an Inflammation State. J Reprod Infertil 2017; 18:352-360. [PMID: 29201665 PMCID: PMC5691251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 06/06/2017] [Indexed: 10/29/2022] Open
Abstract
BACKGROUND Having low-grade chronic inflammation such as elevated C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) plays a crucial role in polycystic ovary syndrome (PCOS). This study aimed at investigating the therapeutic effects of curcumin on IL-6, CRP and TNF-α and symptoms of polycystic ovary syndrome. METHODS In this research, 72 female adult Wistar rats were divided into control (n=12), PCOS (n=12) and curcumin-treated PCOS groups (n=48). PCOS was induced by injection of estradiol valerate (2 mg/kg-one-step). PCOS rats were divided into control and experimental groups which received daily intraperitoneal injection of curcumin. After 60 days of syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 and CRP was detected by the ELISA kit. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA) and p<0.05 was considered statistically significant. RESULTS Histological studies showed a significant reduction in thickness of theca layer and increase in the number of corpus luteum (CL) diameter in the curcumin-treated group compared with the PCOS group; also inflammatory markers such as IL-6 and CRP significantly decreased in groups treated with curcumin compared with PCOS groups. Regarding immunohistochemical analysis, the expression of TNF-α in granulosa layer and follicular fluid of follicles and ovarian cysts in PCOS group was more than the control group's expression. However, expression of this factor in the ovaries treated with curcumin was decreased. CONCLUSION This study showed that the anti-inflammatory and antioxidant effects of curcumin on PCOS may be due to its inhibitory effect on expression and levels of TNF-α, serum IL-6 and CRP.
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Affiliation(s)
- Shima Mohammadi
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Parvin Kayedpoor
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Latifeh Karimzadeh-Bardei
- Laboratory’s Animal Center & Cellular and Molecular Research Laboratory, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Mohammad Nabiuni
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
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Comparative efficacy of epigallocatechin-3-gallate against H 2O 2-induced ROS in cervical cancer biopsies and HeLa cell lines. Contemp Oncol (Pozn) 2017; 21:209-212. [PMID: 29180927 PMCID: PMC5701581 DOI: 10.5114/wo.2017.70110] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Accepted: 06/14/2017] [Indexed: 11/28/2022] Open
Abstract
Aim of the study Antioxidants play an important role in maintaining physiological homeostasis. Recent literature emphasises the potential therapeutic effects of natural antioxidants that play anti-inflammatory and antioxidant effects applicable in preventing oxidative stress-induced injury, which characterises their pathogenesis. The goal of this study was to evaluate the protective role of EGCG on the HeLa cell line and cancerous cells. Material and methods The HeLa cell line and cervical cancer biopsies (CCB) were treated with varying doses of antioxidants to determine their effects. Thereafter, hydrogen peroxide (0–10 nM) – an ROS-generating compound – was co-cultured with varying doses of epigallocatechin-3-gallate (EGCG). The effect of this compound on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity was assessed. Result The activity of SOD and GPx was protected significantly in the treatment of EGCG in cervical cancer biopsies and HeLa cell line. Hypothesis It is hypothesised that EGCG has free radical scavenging properties. Conclusions EGCG protected the activity SOD and GPx equally in cervical cancer biopsies (CCB) and HeLa cell line.
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Hasanpourghadi M, Pandurangan AK, Mustafa MR. Modulation of oncogenic transcription factors by bioactive natural products in breast cancer. Pharmacol Res 2017; 128:376-388. [PMID: 28923544 DOI: 10.1016/j.phrs.2017.09.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 09/11/2017] [Accepted: 09/14/2017] [Indexed: 12/17/2022]
Abstract
Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets. Oncogenic transcription factors resulting from the mutation or overexpression following aberrant gene expression relay the signals in the nucleus and disrupt the transcription pattern. Activation of oncogenic transcription factors is associated with control of cell cycle, apoptosis, migration and cell differentiation. Among different cancer types, breast cancer is one of top ten cancers worldwide. There are different subtypes of breast cancer cell-lines such as non-aggressive MCF-7 and aggressive and metastatic MDA-MB-231 cells, which are identified with distinct molecular profile and different levels of oncogenic transcription factor. For instance, MDA-MB-231 carries mutated and overexpressed p53 with its abnormal, uncontrolled downstream signalling pathway that account for resistance to several anticancer drugs compared to MCF-7 cells with wild-type p53. Appropriate enough, inhibition of oncogenic transcription factors has become a potential target in discovery and development of anti-tumour drugs against breast cancer. Plants produce diverse amount of organic metabolites. Universally, these metabolites with biological activities are known as "natural products". The chemical structure and function of natural products have been studied since 1850s. Investigating these properties leaded to recognition of their molecular effects as anticancer drugs. Numerous natural products extracted from plants, fruits, mushrooms and mycelia, show potential inhibitory effects against several oncogenic transcription factors in breast cancer. Natural compounds that target oncogenic transcription factors have increased the number of candidate therapeutic agents. This review summarizes the current findings of natural products in targeting specific oncogenic transcription factors in breast cancer.
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Affiliation(s)
- Mohadeseh Hasanpourghadi
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Ashok Kumar Pandurangan
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Mohd Rais Mustafa
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia; Centre for Natural Products Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
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41
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Nalli M, Ortar G, Schiano Moriello A, Di Marzo V, De Petrocellis L. Effects of curcumin and curcumin analogues on TRP channels. Fitoterapia 2017; 122:126-131. [PMID: 28903060 DOI: 10.1016/j.fitote.2017.09.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/05/2017] [Accepted: 09/09/2017] [Indexed: 12/28/2022]
Abstract
A series of 33 curcumin analogues was synthesized and tested on TRPA1, TRPM8, and TRPV1 channels. Twenty of them acted as good modulators of TRPA1 channels. None was able to significantly activate TRPM8 channels, while curcumin itself and six curcuminoids belonging to the 1,3-dicarbonyl and acyclic series behaved as 'true' antagonists with IC50 values<5μM. Only few curcuminoids were able to modulate TRPV1 channels with EC50 and IC50 values ranging from 3.4 and 6.0μM.
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Affiliation(s)
- Marianna Nalli
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, piazzale Aldo Moro 5, 00185 Roma, Italy.
| | - Giorgio Ortar
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, piazzale Aldo Moro 5, 00185 Roma, Italy
| | - Aniello Schiano Moriello
- Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, via dei Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | - Vincenzo Di Marzo
- Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, via dei Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy
| | - Luciano De Petrocellis
- Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, via dei Campi Flegrei 34, 80078 Pozzuoli, Napoli, Italy.
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42
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Srinivasan K. Antimutagenic and cancer preventive potential of culinary spices and their bioactive compounds. PHARMANUTRITION 2017. [DOI: 10.1016/j.phanu.2017.06.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Yamaguchi T, Yoneyama M, Onaka Y, Imaizumi A, Ogita K. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study. J Pharmacol Sci 2017; 134:225-233. [DOI: 10.1016/j.jphs.2017.07.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 07/20/2017] [Accepted: 07/28/2017] [Indexed: 11/16/2022] Open
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Kuguacin J isolated from bitter melon leaves modulates paclitaxel sensitivity in drug-resistant human ovarian cancer cells. J Nat Med 2017. [PMID: 28639112 DOI: 10.1007/s11418-017-1099-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
We previously reported the multidrug resistance-reversing ability of kuguacin J (KJ) in cervical cancer cells via the inhibition of P-glycoprotein (P-gp) function. This study investigated whether KJ could promote cisplatin- and paclitaxel (PTX)-induced cancer cell death in drug-resistance human ovarian cancer cells (SKOV3). Cytotoxicity testing showed that SKOV3 was more resistant to cisplatin and PTX compared to drug-sensitive human ovarian cancer cells (A2780). The cytotoxicity of PTX was significantly increased in SKOV3 cells when co-treated with KJ. We found that enhancement of PTX toxicity in the cells was not related to P-gp inhibition. To elucidate the mechanism by which KJ increases PTX sensitivity, the expression of cell death involving proteins was analyzed by Western blot analysis. The results showed that PTX treatment increased the level of an anti-apoptotic protein, survivin, which may be involved in drug resistance in SKOV3. The co-treatment with PTX and KJ dramatically decreased the level of survivin and markedly induced cleavage of PARP and caspase-3, which are apoptotic-induced molecules. These findings may support the use of KJ as an effective chemosensitizer in combination with conventional chemotherapy to promote PTX sensitization in ovarian cancer patients.
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Wu X, Song M, Gao Z, Sun Y, Wang M, Li F, Zheng J, Xiao H. Nobiletin and its colonic metabolites suppress colitis-associated colon carcinogenesis by down-regulating iNOS, inducing antioxidative enzymes and arresting cell cycle progression. J Nutr Biochem 2017; 42:17-25. [DOI: 10.1016/j.jnutbio.2016.12.020] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 11/29/2016] [Accepted: 12/28/2016] [Indexed: 12/11/2022]
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Mollaei H, Babaei E. Therapeutic Potential of Novel Nano-Based Curcumin
Compounds In Vitro and In Vivo. Asian Pac J Cancer Prev 2017; 18:885-888. [PMID: 28545183 PMCID: PMC5494236 DOI: 10.22034/apjcp.2017.18.4.885] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Despite recent advances in cancer medication, malignant tumors continue to be the second leading cause of death worldwide. Furthermore, introducing a therapeutic compound with low-side effects as well as low-price for consumers is controversial. Recent efforts have been focusing on traditional medicines as a rich source of herbal agents. Curcumin, the major turmeric phytochemical, has been widely assessed as an anti-cancer compound in vitro and in vivo. However, the use of curcumin in cancer treatment has limitations because of its low solubility, poor tissue absorption, rapid metabolism and rapid systemic elimination. Recent work has focused on improving the stability of curcumin to facilitate clinical application. Dendrosomal nano-corcumin (DNC) is one of the most successful compounds showing significant cellular absorption and also anti-tumor effects. The present overview of newest applicable strategies for curcumin-based therapy and their clinical potential usefulness has the emphasis on DNC.
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Affiliation(s)
- Homa Mollaei
- Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran.
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Wang L, Chen X, Du Z, Li G, Chen M, Chen X, Liang G, Chen T. Curcumin suppresses gastric tumor cell growth via ROS-mediated DNA polymerase γ depletion disrupting cellular bioenergetics. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2017; 36:47. [PMID: 28359291 PMCID: PMC5374654 DOI: 10.1186/s13046-017-0513-5] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Accepted: 03/10/2017] [Indexed: 02/08/2023]
Abstract
Background Curcumin, as a pro-apoptotic agent, is extensively studied to inhibit tumor cell growth of various tumor types. Previous work has demonstrated that curcumin inhibits cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of curcumin in regulating cellular bioenergetic processes remains largely unknown. Methods Western blotting and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively. RTCA, CCK-8 assay, nude mice xenograft assay, and in vivo bioluminescence imaging were used to visualize the effects of curcmin on gastric cancer cell growth in vitro and in vivo. Seahorse bioenergetics analyzer was used to investigate the alteration of oxygen consumption and aerobic glycolysis rate. Results Curcumin significantly inhibited gastric tumor cell growth, proliferation and colony formation. We further investigated the role of curcumin in regulating cellular redox homeostasis and demonstrated that curcumin initiated severe cellular apoptosis via disrupting mitochondrial homeostasis, thereby enhancing cellular oxidative stress in gastric cancer cells. Furthermore, curcumin dramatically decreased mtDNA content and DNA polymerase γ (POLG) which contributed to reduced mitochondrial oxygen consumption and aerobic glycolysis. We found that curcumin induced POLG depletion via ROS generation, and POLG knockdown also reduced oxidative phosphorylation (OXPHOS) activity and cellular glycolytic rate which was partially rescued by ROS scavenger NAC, indiating POLG plays an important role in the treatment of gastric cancer. Data in the nude mice model verified that curcumin treatment significantly attenuated tumor growth in vivo. Finally, POLG was up-regulated in human gastric cancer tissues and primary gastric cancer cell growth was notably suppressed due to POLG deficiency. Conclusions Together, our data suggest a novel mechanism by which curcumin inhibited gastric tumor growth through excessive ROS generation, resulting in depletion of POLG and mtDNA, and the subsequent disruption of cellular bioenergetics.
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Affiliation(s)
- Lihua Wang
- Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, China.,State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of the People's Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.,School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiwen Chen
- Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhuanyun Du
- School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Gefei Li
- School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mayun Chen
- Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China
| | - Xi Chen
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Guang Liang
- Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. .,Wenzhou Medical University, University-Town, Wenzhou, Zhejiang, 325035, China.
| | - Tongke Chen
- Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, Zhejiang, China. .,Wenzhou Medical University, University-Town, Wenzhou, Zhejiang, 325035, China.
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48
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Campbell MS, Berrones AJ, Krishnakumar I, Charnigo RJ, Westgate PM, Fleenor BS. Responsiveness to curcumin intervention is associated with reduced aortic stiffness in young, obese men with higher initial stiffness. J Funct Foods 2017. [DOI: 10.1016/j.jff.2016.12.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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49
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Chen L, Teng H, Zhang KY, Skalicka-Woźniak K, Georgiev MI, Xiao J. Agrimonolide and Desmethylagrimonolide Induced HO-1 Expression in HepG2 Cells through Nrf2-Transduction and p38 Inactivation. Front Pharmacol 2017; 7:513. [PMID: 28119605 PMCID: PMC5223292 DOI: 10.3389/fphar.2016.00513] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 12/12/2016] [Indexed: 02/05/2023] Open
Abstract
Agrimonolide and desmethylagrimonolide are the main bioactive polyphenols in agrimony with well-documented antioxidant, anti-diabetic, and anti-inflammatory potential. We report here for the first time that agrimonolide and desmethylagrimonolide stimulate the expression of phase II detoxifying enzymes through the Nrf2-dependent signaling pathway. Agrimonolide and desmethylagrimonolide also possess considerable protective activity from oxidative DNA damage. In order to explore the cytoprotective potential of agrimonolide and desmethylagrimonolide on oxidative stress in liver, we developed an oxidative stress model in HepG2 cells, and check the hypothesis whether Nrf2 pathway is involved. Western blotting and luciferase assay revealed that exposure of HepG2 cells to agrimonolide or desmethylagrimonolide leads to increased heme oxygenase-1 (HO-1) expression by activating ARE through induction of Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). Moreover, agrimonolide and desmethylagrimonolide also activated ERK signaling pathways and significantly attenuated individual p38 MAPK expression, subsequently leading to Nrf2 nuclear translocation. In conclusion, our results indicated that transcriptional activation of Nrf2/ARE is critical in agrimonolide and desmethylagrimonolide-mediated HO-1 induction, which can be regulated partially by the blockade of p38 MAPK signaling pathway and inhibiting nuclear translocation of Nrf2.
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Affiliation(s)
- Lei Chen
- College of Food Science, Fujian Agriculture and Forestry University Fuzhou, China
| | - Hui Teng
- College of Food Science, Fujian Agriculture and Forestry University Fuzhou, China
| | - Kalin Yanbo Zhang
- School of Chinese Medicine, The University of Hong Kong Hong Kong, Hong Kong
| | | | - Milen I Georgiev
- Group of Plant Cell Biotechnology and Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences Plovdiv, Bulgaria
| | - Jianbo Xiao
- College of Food Science, Fujian Agriculture and Forestry UniversityFuzhou, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauTaipa, Macau
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50
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Hu XQ, Sun Y, Lau E, Zhao M, Su SB. Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer. Curr Cancer Drug Targets 2016; 16:346-56. [PMID: 26638885 PMCID: PMC5425653 DOI: 10.2174/1568009616666151207105851] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 09/15/2015] [Accepted: 12/04/2015] [Indexed: 12/13/2022]
Abstract
The complex pathology of cancer development requires correspondingly complex treatments. The traditional application of individual single-target drugs fails to sufficiently treat cancer with durable therapeutic effects and tolerable adverse events. Therefore, synergistic combinations of drugs represent a promising way to enhance efficacy, overcome toxicity and optimize safety. Chinese Herbal Medicines (CHMs) have long been used as such synergistic combinations. Therefore, we summarized the synergistic combinations of CHMs used in the treatment of cancer and their roles in chemotherapy in terms of enhancing efficacy, reducing side effects, immune modulation, as well as abrogating drug resistance. Our conclusions support the development of further science-based holistic modalities for cancer care.
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Affiliation(s)
| | | | | | | | - Shi-Bing Su
- Department of Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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