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Yu X, Wu W, Hao J, Zhou Y, Yu D, Ding W, Zhang X, Liu G, Wang J. Ginger protects against vein graft remodeling by precisely modulating ferroptotic stress in vascular smooth muscle cell dedifferentiation. J Pharm Anal 2025; 15:101053. [PMID: 39974619 PMCID: PMC11835576 DOI: 10.1016/j.jpha.2024.101053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 06/28/2024] [Accepted: 07/22/2024] [Indexed: 02/21/2025] Open
Abstract
Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.
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Affiliation(s)
- Xiaoyu Yu
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China
| | - Weiwei Wu
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China
| | - Jingjun Hao
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China
| | - Yuxin Zhou
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China
| | - Deyang Yu
- Department of Emergency Surgery, Qingdao Central Hospital, Qingdao, Shandong, 266071, China
| | - Wei Ding
- Department of General Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266071, China
| | - Xuejuan Zhang
- Department of General Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266071, China
| | - Gaoli Liu
- Department of Cardiac Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266071, China
| | - Jianxun Wang
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China
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Kim H, Shin J, Lee Y, Jin B, Lee WW, Lee Y, Choi S, Han J, Ahn M, Kim J, Park D, Hong S, Kang S, Cho S. Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein. Cancer Sci 2024; 115:2701-2717. [PMID: 38888067 PMCID: PMC11309930 DOI: 10.1111/cas.16248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 05/23/2024] [Accepted: 06/03/2024] [Indexed: 06/20/2024] Open
Abstract
The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.
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Affiliation(s)
- Hyun‐Ji Kim
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Ji‐Ae Shin
- Department of OtorhinolaryngologyYonsei University College of MedicineSeoulRepublic of Korea
| | - Yeong‐Geun Lee
- Department of Oriental Medicine Biotechnology, College of Life ScienceKyung Hee UniversityYonginRepublic of Korea
| | - Bohwan Jin
- Laboratory Animal CenterCHA UniversitySeongnamRepublic of Korea
| | - Won Woo Lee
- Laboratory Animal CenterCHA UniversitySeongnamRepublic of Korea
| | - Yosub Lee
- Department of Oral Pathology, School of DentistrySeoul National UniversitySeoulRepublic of Korea
| | - Su‐Jung Choi
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Jung‐Min Han
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Min‐Hye Ahn
- Chemical Biology Research CenterKorea Research Institute of Bioscience and BiotechnologyCheongjuRepublic of Korea
| | - Ji‐Hoon Kim
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Dong‐Guk Park
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Seong‐Doo Hong
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
| | - Se‐Chan Kang
- Department of Oriental Medicine Biotechnology, College of Life ScienceKyung Hee UniversityYonginRepublic of Korea
| | - Sung‐Dae Cho
- Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea
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International BR. Retracted: Differential Control of Growth, Apoptotic Activity, and Gene Expression in Human Breast Cancer Cells by Extracts Derived from Medicinal Herbs Zingiber officinale. BIOMED RESEARCH INTERNATIONAL 2023; 2023:9838617. [PMID: 36650827 PMCID: PMC9840901 DOI: 10.1155/2023/9838617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 11/25/2022] [Indexed: 01/09/2023]
Abstract
[This retracts the article DOI: 10.1155/2012/614356.].
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Usman AN, Manju B, Ilhamuddin I, Ahmad M, Ab T, Ariyandy A, Budiaman B, Eragradini AR, Hasan II, Hashim S, Sartini S, Sinrang AW. Ginger potency on the prevention and treatment of breast cancer. Breast Dis 2023; 42:207-212. [PMID: 37424457 DOI: 10.3233/bd-239003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
BACKGROUND Cancer is a type of disease caused by the uncontrolled growth of abnormal cells that can destroy body tissues. The use of traditional medicine naturally uses plants from ginger with the maceration method. The ginger plant is a herbaceous flowering plant with the Zingiberaceacea group. METHODS This study uses the literature review method by reviewing 50 articles from journals and databases. RESULTS A review of several articles, namely ginger has bioactive components such as gingerol. Ginger is used as a treatment in complementary therapies using plants. Ginger is a strategy with many benefits and functions as a nutritional complement to the body. This benefit has shown the effect of anti-inflammatory, antioxidant, and anticancer against nausea and vomiting due to chemotherapy in breast cancer. CONCLUSION Anticancer in ginger is shown by polyphenols associated with anti-metastatic, anti-proliferative, antiangiogenic, anti-inflammatory, cell cycle arrest, apoptosis, and autophagy. Therefore, consuming ginger regularly affects natural herbal therapy with the prevention and treatment of breast cancer and serves as a prevention against the effects of chemotherapy.
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Affiliation(s)
- Andi Nilawati Usman
- Department of Midwifery, Graduate School, Hasanuddin University, Makassar, Indonesia
| | - Budu Manju
- Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | | | - Mardiana Ahmad
- Department of Midwifery, Graduate School, Hasanuddin University, Makassar, Indonesia
| | - Takko Ab
- Cultural Science, Hasanuddin University, Makassar, Indonesia
| | - Andi Ariyandy
- Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
| | | | | | | | | | - Sartini Sartini
- Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
| | - Andi Wardihan Sinrang
- Department of Midwifery, Graduate School, Hasanuddin University, Makassar, Indonesia
- Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
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Al Mousa AA, Abouelela ME, Hassane AMA, Al-Khattaf FS, Hatamleh AA, Alabdulhadi HS, Dahmash ND, Abo-Dahab NF. Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation. Curr Issues Mol Biol 2022; 44:5067-5085. [PMID: 36286059 PMCID: PMC9600980 DOI: 10.3390/cimb44100344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/16/2022] [Accepted: 10/17/2022] [Indexed: 11/23/2022] Open
Abstract
Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 μg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (-8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4'-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy.
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Affiliation(s)
- Amal A. Al Mousa
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia
| | - Mohamed E. Abouelela
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40506, USA
| | - Abdallah M. A. Hassane
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt
| | - Fatimah S. Al-Khattaf
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia
| | - Ashraf A. Hatamleh
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia
| | - Hadeel S. Alabdulhadi
- Research Assistant Internship Program, Vice Rectorate for Graduate Studies and Scientific Research, King Saud University, Deanship of Scientific Research, Riyadh 4545, Saudi Arabia
| | - Noura D. Dahmash
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia
| | - Nageh F. Abo-Dahab
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt
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In Vitro Cytotoxicity and Spectral Analysis-Based Phytochemical Profiling of Methanol Extract of Barleria hochstetteri, and Molecular Mechanisms Underlying Its Apoptosis-Inducing Effect on Breast and Lung Cancer Cell Lines. SEPARATIONS 2022. [DOI: 10.3390/separations9100298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The objectives of this research were to carry out GC–MS and LC–MS-based phytochemical profiling of Barleria hochstetteri, as well as flow cytometry-based mechanistic investigations of the cytotoxic effect of its extracts against breast and lung cancer cell lines. This preclinical in vitro study was carried out in Saudi Arabia and India, from 11 August to 15 January 2022. Barleria hochstetteri was sequentially extracted using the Soxhlet extraction technique. Utilizing LC–MS and GC–MS methods, the phytochemical profiling was performed. Additionally, the total phenolic compounds and flavonoids were quantified in the plant extract using spectrophotometric techniques. In this study, we first examined the cytotoxicity of the plant extract on non-malignant L929 cells and on the carcinogenic MCF-7 and A549 cell lines. Then, we studied the underlying molecular pathways by means of Anti-Bcl-2, caspase-3, and DNA fragmentation (TUNEL) assays, using flow cytometry. The results revealed phenolic compounds and flavonoids to be the two major components in the methanolic extract of B. hochstetteri, with concentrations of 3210 µg GAE/g dwt and 1863 µg QE/g dwt, respectively. Results from GC–MS and LC–MS analyses revealed the presence of bioactive phytochemicals with known cytotoxicity. From the MTT assay on cell viability, the IC50 of the methanol extract for the MCF-7 and A549 cell lines were 219.67 and 144.30 µg/mL, respectively. With IC50 values of 324.24 and 266.66 µg/mL, respectively, the aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line. The extract caused early and late apoptosis in the tested breast and lung cancer cells by activating caspase-3 and inhibiting Bcl-2 protein, and it also caused cell death via DNA damage, based on flow cytometric and molecular marker analyses. These findings indicate that the methanol extract of B. hochstetteri was cytotoxic on breast cancer and lung cancer cell lines. To uncover cancer-fighting chemicals, there is a need for further research on B. hochstetteri, as it is a promising source of anti-cancer chemotherapeutic drugs.
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Kim SD, Kwag EB, Yang MX, Yoo HS. Efficacy and Safety of Ginger on the Side Effects of Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis. Int J Mol Sci 2022; 23:11267. [PMID: 36232567 PMCID: PMC9569531 DOI: 10.3390/ijms231911267] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/18/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
Cancer is one of the leading causes of death in the world, with breast cancer being the most prevalent cancer. Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious side effects of chemotherapy. Because the current CINV treatment option has several flaws, alternative treatment options are required. Ginger has traditionally been used to treat nausea and vomiting, and it also has anticancer properties in breast cancer cells. Based on these findings, researchers investigated whether using ginger to treat CINV in breast cancer patients is both effective and safe. We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang from inception to June 2022. Outcomes included Rhodes Index Scores of Nausea, Vomiting, and Retching, severity and frequency of CINV. Five RCTs were included. We pooled all included data and performed subgroup analysis by types of CINV. Overall, authors found that ginger was associated with a reduction in CINV. Subgroup and sensitivity analysis revealed that managing severity of acute CINV in breast cancer patients with ginger was efficient. In terms of managing delayed CINV in breast cancer patients, ginger was also statistically significant. The authors concluded that ginger may be helpful in lowering both acute and delayed CINV in breast cancer patients. Since there were no serious side effects, ginger is thought to be safe.
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Affiliation(s)
- Soo-Dam Kim
- College of Korean Medicine, Daejeon University, Daejeon 34520, Korea
- Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, Department of Medicine, 321 E 61st Street, New York, NY 10065, USA
| | - Eun-Bin Kwag
- College of Korean Medicine, Daejeon University, Daejeon 34520, Korea
- East West Cancer Center, Daejeon Korean Medicine Hospital, Daejeon University, Daejeon 35235, Korea
| | - Ming-Xiao Yang
- Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, Department of Medicine, 321 E 61st Street, New York, NY 10065, USA
| | - Hwa-Seung Yoo
- East West Cancer Center, Seoul Korean Medicine Hospital, Daejeon University, Seoul 05836, Korea
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Khan MI, Karima G, Khan MZ, Shin JH, Kim JD. Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. Int J Mol Sci 2022; 23:10665. [PMID: 36142578 PMCID: PMC9504392 DOI: 10.3390/ijms231810665] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/06/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.
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Affiliation(s)
- Muhammad Imran Khan
- Department of Biotechnology, Faculty of Biomedical and Life Sciences, Kohsar University, Murree 47150, Pakistan
| | - Gul Karima
- Department of Bionanotechnology, Graduate School, Hanyang University, Seoul 04763, Korea
| | | | - Jin Hyuk Shin
- Department of Biotechnology, Chonnam National University, Yeosu 59626, Korea
| | - Jong Deog Kim
- Department of Biotechnology, Chonnam National University, Yeosu 59626, Korea
- Research Center on Anti-Obesity and Health Care, Chonnam National University, Yeosu 59626, Korea
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Synthesis and Biological Evaluation of Indole-2-Carboxamides with Potent Apoptotic Antiproliferative Activity as EGFR/CDK2 Dual Inhibitors. Pharmaceuticals (Basel) 2022; 15:ph15081006. [PMID: 36015154 PMCID: PMC9414584 DOI: 10.3390/ph15081006] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/10/2022] [Accepted: 08/10/2022] [Indexed: 11/28/2022] Open
Abstract
The apoptotic antiproliferative actions of our previously reported CB1 allosteric modulators 5-chlorobenzofuran-2-carboxamide derivatives VIIa–j prompted us to develop and synthesise a novel series of indole-2-carboxamide derivatives 5a–k, 6a–c, and 7. Different spectroscopic methods of analysis were used to validate the novel compounds. Using the MTT assay method, the novel compounds were examined for antiproliferative activity against four distinct cancer cell lines. Compounds 5a–k, 6a–c, and 7 demonstrated greater antiproliferative activity against the breast cancer cell line (MCF-7) than other tested cancer cell lines, and 5a–k (which contain the phenethyl moiety in their backbone structure) demonstrated greater potency than 6a–c and 7, indicating the importance of the phenethyl moiety for antiproliferative action. Compared to reference doxorubicin (GI50 = 1.10 µM), compounds 5d, 5e, 5h, 5i, 5j, and 5k were the most effective of the synthesised derivatives, with GI50 ranging from 0.95 µM to 1.50 µM. Compounds 5d, 5e, 5h, 5i, 5j, and 5k were tested for their inhibitory impact on EGFR and CDK2, and the results indicated that the compounds tested had strong antiproliferative activity and are effective at suppressing both CDK2 and EGFR. Moreover, the studied compounds induced apoptosis with high potency, as evidenced by their effects on apoptotic markers such as Caspases 3, 8, 9, Cytochrome C, Bax, Bcl2, and p53.
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Shrihastini V, Muthuramalingam P, Adarshan S, Sujitha M, Chen JT, Shin H, Ramesh M. Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview. Cancers (Basel) 2021; 13:cancers13246222. [PMID: 34944840 PMCID: PMC8699774 DOI: 10.3390/cancers13246222] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer is one of the most common malignant diseases that occur worldwide, among which breast cancer is the second leading cause of death in women. The subtypes are associated with differences in the outcome and were selected for treatments according to the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor. Triple-negative breast cancer, one of the subtypes of breast cancer, is difficult to treat and can even lead to death. If breast cancer is not treated during the initial stages, it may spread to nearby organs, a process called metastasis, through the blood or lymph system. For in vitro studies, MCF-7, MDA-MB-231, MDA-MB-468, and T47B are the most commonly used breast cancer cell lines. Clinically, chemotherapy and radiotherapy are usually expensive and can also cause side effects. To overcome these issues, medicinal plants could be the best alternative for chemotherapeutic drugs with fewer side effects and cost-effectiveness. Furthermore, the genes involved in breast cancer can be regulated and synergized with signaling molecules to suppress the proliferation of breast cancer cells. In addition, nanoparticles encapsulating (nano-encapsulation) medicinal plant extracts showed a significant reduction in the apoptotic and cytotoxic activities of breast cancer cells. This present review mainly speculates an overview of the native medicinal plant derived anti-cancerous compounds with its efficiency, types and pathways involved in breast cancer along with its genes, the mechanism of breast cancer brain metastasis, chemoresistivity and its mechanism, bioinformatics approaches which could be an effective alternative for drug discovery.
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Affiliation(s)
- Vijayakumar Shrihastini
- Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India; (V.S.); (M.S.)
| | - Pandiyan Muthuramalingam
- Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India; (V.S.); (M.S.)
- Correspondence: (P.M.); (J.-T.C.)
| | - Sivakumar Adarshan
- Department of Biotechnology, Science Campus, Alagappa University, Karaikudi 630003, Tamil Nadu, India; (S.A.); (M.R.)
| | - Mariappan Sujitha
- Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India; (V.S.); (M.S.)
| | - Jen-Tsung Chen
- Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan
- Correspondence: (P.M.); (J.-T.C.)
| | - Hyunsuk Shin
- Department of Horticultural Sciences, Gyeongsang National University, Jinju 52725, Korea;
| | - Manikandan Ramesh
- Department of Biotechnology, Science Campus, Alagappa University, Karaikudi 630003, Tamil Nadu, India; (S.A.); (M.R.)
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Anjum S, Hashim M, Malik SA, Khan M, Lorenzo JM, Abbasi BH, Hano C. Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment. Cancers (Basel) 2021; 13:4570. [PMID: 34572797 PMCID: PMC8468934 DOI: 10.3390/cancers13184570] [Citation(s) in RCA: 157] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer is regarded as one of the most deadly and mirthless diseases and it develops due to the uncontrolled proliferation of cells. To date, varieties of traditional medications and chemotherapies have been utilized to fight tumors. However, their immense drawbacks, such as reduced bioavailability, insufficient supply, and significant adverse effects, make their use limited. Nanotechnology has evolved rapidly in recent years and offers a wide spectrum of applications in the healthcare sectors. Nanoscale materials offer strong potential for curing cancer as they pose low risk and fewer complications. Several metal oxide NPs are being developed to diagnose or treat malignancies, but zinc oxide nanoparticles (ZnO NPs) have remarkably demonstrated their potential in the diagnosis and treatment of various types of cancers due to their biocompatibility, biodegradability, and unique physico-chemical attributes. ZnO NPs showed cancer cell specific toxicity via generation of reactive oxygen species and destruction of mitochondrial membrane potential, which leads to the activation of caspase cascades followed by apoptosis of cancerous cells. ZnO NPs have also been used as an effective carrier for targeted and sustained delivery of various plant bioactive and chemotherapeutic anticancerous drugs into tumor cells. In this review, at first we have discussed the role of ZnO NPs in diagnosis and bio-imaging of cancer cells. Secondly, we have extensively reviewed the capability of ZnO NPs as carriers of anticancerous drugs for targeted drug delivery into tumor cells, with a special focus on surface functionalization, drug-loading mechanism, and stimuli-responsive controlled release of drugs. Finally, we have critically discussed the anticancerous activity of ZnO NPs on different types of cancers along with their mode of actions. Furthermore, this review also highlights the limitations and future prospects of ZnO NPs in cancer theranostic.
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Affiliation(s)
- Sumaira Anjum
- Department of Biotechnology, Kinnaird College for Women, Jail Road, Lahore 54000, Pakistan; (M.H.); (S.A.M.); (M.K.)
| | - Mariam Hashim
- Department of Biotechnology, Kinnaird College for Women, Jail Road, Lahore 54000, Pakistan; (M.H.); (S.A.M.); (M.K.)
| | - Sara Asad Malik
- Department of Biotechnology, Kinnaird College for Women, Jail Road, Lahore 54000, Pakistan; (M.H.); (S.A.M.); (M.K.)
| | - Maha Khan
- Department of Biotechnology, Kinnaird College for Women, Jail Road, Lahore 54000, Pakistan; (M.H.); (S.A.M.); (M.K.)
| | - José M. Lorenzo
- Centro Tecnológico de la Carne de Galicia, Avenida de Galicia 4, Parque Tecnológico de Galicia, 32900 San Cibrao das Viñas, Ourense, Spain;
- Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, Universidad de Vigo, 32004 Ourense, Spain
| | - Bilal Haider Abbasi
- Department of Biotechnology, Quaid-i-Azam University, Islamabad 15320, Pakistan;
| | - Christophe Hano
- Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRAE USC1328, Eure & Loir Campus, University of Orleans, 28000 Chartres, France;
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12
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Dehimat A, Azizi I, Barragan-Montero V, Khettal B. Cytotoxicity and antioxidant activities of leaf extracts of Varthemia sericea (Batt. et Trab.) Diels. Eur J Integr Med 2021. [DOI: 10.1016/j.eujim.2021.101338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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13
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Mathiyazhagan J, Siva R, Jayaraj R, Madhyastha H, Kodiveri Muthukaliannan G. Preventive Effect of Combined Zingiber officinale and Terminalia chebula against DMBA-Induced Breast Cancer Rats via mTOR Inhibition. Nutr Cancer 2021; 74:687-696. [PMID: 33821702 DOI: 10.1080/01635581.2021.1903948] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 02/24/2021] [Accepted: 02/28/2021] [Indexed: 10/21/2022]
Abstract
Zingiber officinale (ZO) and Terminalia chebula (TC) are plants used for the treatment of diverse illnesses in traditional medicine. The present study investigates the preventive effect of Zingiber officinale-Terminalia chebula extract (ZOTC) against DMBA-induced breast cancer in a rat model. Bioactive compounds from ZO (6-gingerol, 6-shogaol) and TC (gallic acid, ellagic acid, corilagin, chebulinic acid, and chebulagic acid) were detected using high-performance liquid chromatography. Mammary carcinogenesis was induced in rats with a single subcutaneous injection of 7,12-Dimethylbenz[a]anthracene (DMBA). Oral administration of ZOTC ameliorated the antioxidant status in mammary tissues, serum lipid levels, and serum cytokines. Histological analysis of the mammary tissue (normal and tumor) was carried out to obtain pathological alterations due to ZOTC treatment. The effect of ZOTC on the mechanistic target of rapamycin (mTOR) gene and accumulation of corresponding gene product was also investigated. mTOR plays a central role in cell metabolism and proliferation in normal and cancer cells. Transcriptional and immunohistochemical analysis showed the downregulation of mTOR expression in the mammary tissues of ZOTC-treated rats. In conclusion, the results obtained suggest that ZOTC can suppress tumor progression in DMBA-induced breast cancer rats via inhibition of the mTOR pathway.
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Affiliation(s)
- Jayasindu Mathiyazhagan
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore-14, Tamil Nadu, India
| | - Ramamoorthy Siva
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore-14, Tamil Nadu, India
| | - Rama Jayaraj
- Northern Territory Institute of Research and Training, Theme lead, Flinders NT, Flinders University, Northern Territory, Australia
| | - Harishkumar Madhyastha
- Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Gothandam Kodiveri Muthukaliannan
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore-14, Tamil Nadu, India
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14
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Gospodinova ZI, Zupkó I, Bózsity N, Manova VI, Georgieva MS, Todinova SJ, Taneva SG, Ocsovszki I, Krasteva ME. Cotinus coggygria Scop. induces cell cycle arrest, apoptosis, genotoxic effects, thermodynamic and epigenetic events in MCF7 breast cancer cells. ACTA ACUST UNITED AC 2021; 76:129-140. [PMID: 32975208 DOI: 10.1515/znc-2020-0087] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 09/05/2020] [Indexed: 12/24/2022]
Abstract
Current plant-derived anticancer therapeutics aim to reach higher effectiveness, to potentiate chemosensitivity and minimize the toxic side effects compared to conventional chemotherapy. Cotinus coggygria Scop. is a herb with high pharmacological potential, widely applied in traditional phytotherapy. Our previous study revealed that leaf aqueous ethanolic extract from C. coggygria exerts in vitro anticancer activity on human breast, ovarian and cervical cancer cell lines. The objective of the present research was to investigate possible molecular mechanisms and targets of the antitumor activity of the extract in breast cancer MCF7 cells through analysis of cell cycle and apoptosis, clonogenic ability assessment, evaluation of the extract genotoxic capacity, characterization of cells thermodynamic properties, and analysis on the expression of genes involved in cellular epigenetic processes. The obtained results indicated that in MCF7 cells C. coggygria extract causes S phase cell cycle arrest and triggers apoptosis, reduces colony formation, induces DNA damage, affects cellular thermodynamic parameters, and tends to inhibit the relative expression of DNMT1, DNMT3a, MBD3, and p300. Further studies on the targeted molecules and the extract anti-breast cancer potential on animal experimental model system, need to be performed in the future.
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Affiliation(s)
- Zlatina I Gospodinova
- Laboratory of Genome Dynamics and Stability, Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
| | - Istvan Zupkó
- Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eotvos Str. 6, H-6720 Szeged, Hungary
| | - Noémi Bózsity
- Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eotvos Str. 6, H-6720 Szeged, Hungary
| | - Vasilissa I Manova
- Laboratory of Genome Dynamics and Stability, Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
| | - Mariyana S Georgieva
- Laboratory of Regulation of Gene Expression, Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
| | - Svetla J Todinova
- Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
| | - Stefka G Taneva
- Department of Biomacromolecules and Biomolecular Interactions, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
| | - Imre Ocsovszki
- Department of Biochemistry, University of Szeged, Dóm tér 9, H-6720 Szeged, Hungary
| | - Maria E Krasteva
- Laboratory of Genome Dynamics and Stability, Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bldg. 21, 1113 Sofia, Bulgaria
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15
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Kiyama R. Nutritional implications of ginger: chemistry, biological activities and signaling pathways. J Nutr Biochem 2020; 86:108486. [PMID: 32827666 DOI: 10.1016/j.jnutbio.2020.108486] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 06/01/2020] [Accepted: 08/05/2020] [Indexed: 12/30/2022]
Abstract
Ginger (Zingiber officinale Roscoe) has been used as a food, spice, supplement and flavoring agent and in traditional medicines due to its beneficial characteristics such as pungency, aroma, nutrients and pharmacological activity. Ginger and ginger extracts were reported to have numerous effects, such as those on diabetes and metabolic syndrome, cholesterol levels and lipid metabolism, and inflammation, revealed by epidemiological studies. To understand the beneficial characteristics of ginger, especially its physiological and pharmacological activities at the molecular level, the biological effects of ginger constituents, such as monoterpenes (cineole, citral, limonene and α/β-pinenes), sesquiterpenes (β-elemene, farnesene and zerumbone), phenolics (gingerols, [6]-shogaol, [6]-paradol and zingerone) and diarylheptanoids (curcumin), and the associated signaling pathways are summarized. Ginger constituents are involved in biological activities, such as apoptosis, cell cycle/DNA damage, chromatin/epigenetic regulation, cytoskeletal regulation and adhesion, immunology and inflammation, and neuroscience, and exert their effects through specific signaling pathways associated with cell functions/mechanisms such as autophagy, cellular metabolism, mitogen-activated protein kinase and other signaling, and development/differentiation. Estrogens, such as phytoestrogens, are one of the most important bioactive materials in nature, and the molecular mechanisms of estrogen actions and the assays to detect them have been discussed. The molecular mechanisms of estrogen actions induced by ginger constituents and related applications, such as the chemoprevention of cancers, and the improvement of menopausal syndromes, osteoporosis, endometriosis, prostatic hyperplasia, polycystic ovary syndrome and Alzheimer's disease, were summarized by a comprehensive search of references to understand more about their health benefits and associated health risks.
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Affiliation(s)
- Ryoiti Kiyama
- Department of Life Science, Faculty of Life Science, Kyushu Sangyo Univ., 2-3-1 Matsukadai, Higashi-ku, Fukuoka 813-8503, Japan.
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16
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Marmitt DJ, Bitencourt S, Silva GRD, Rempel C, Goettert MI. RENISUS Plants and Their Potential Antitumor Effects in Clinical Trials and Registered Patents. Nutr Cancer 2020; 73:1821-1848. [PMID: 32835511 DOI: 10.1080/01635581.2020.1810290] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 08/08/2020] [Accepted: 08/09/2020] [Indexed: 12/18/2022]
Abstract
Cancer is a significant cause of morbidity and mortality. Scientific advances, coupled with potential flaws in current treatments, are driving research into the discovery of new bioactive molecules. This systematic review focused on scientific studies with clinical trials and patents registered on the National Relation of Medicinal Plants of Interest to the Unified Health System (RENISUS) plants (or derivative compounds) with antitumor potential. Studies with 19 different forms of cancer were found, the prostate being the organ with the highest research incidence and the species Glycine max, Curcuma longa, and Zingiber officinale, beside the phytochemicals curcumin and soy isoflavone were the most tested in clinical trials/patents.
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Affiliation(s)
- Diorge Jônatas Marmitt
- Laboratório de Cultura de Células, Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, Brazil
| | - Shanna Bitencourt
- Laboratório de Cultura de Células, Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, Brazil
| | - Gustavo Rodrigo da Silva
- Centro de Ciências Biológicas e da Saúde, Universidade do Vale do Taquari (Univates), Lajeado, Brazil
| | - Claudete Rempel
- Programa de Pós-graduação em Ambiente e Desenvolvimento/Programa de Pós-graduação em Sistemas Ambientais Sustentáveis, Universidade do Vale do Taquari (Univates), Lajeado, Brazil
| | - Márcia Inês Goettert
- Laboratório de Cultura de Células, Programa de Pós-graduação em Biotecnologia, Universidade do Vale do Taquari (Univates), Lajeado, Brazil
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17
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Mathiyazhagan J, Kodiveri Muthukaliannan G. Combined Zingiber officinale and Terminalia chebula Induces Apoptosis and Modulates mTOR and hTERT Gene Expressions in MCF-7 Cell Line. Nutr Cancer 2020; 73:1207-1216. [PMID: 32664754 DOI: 10.1080/01635581.2020.1792518] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 06/23/2020] [Accepted: 06/23/2020] [Indexed: 12/24/2022]
Abstract
In this study, we evaluated the cytotoxicity and apoptotic activity of Zingiber officinale (ZO), Terminalia chebula (TC) alone, and in combination (ZO:TC-1:4). The presence of major bioactive compounds in ZO (6-gingerol and 6-shogaol) and TC (gallic acid, ellagic acid, and chebulinic acid) were evaluated by high performance liquid chromatography. The IC50 values of ZO, TC, and ZOTC (1:4) was estimated to be 88.5, 108.5, and 53.5 μg/mL, respectively. The cell death and cytomorphology changes upon treatment were observed. At these concentrations, ZO, TC, and ZOTC showed reduced mitochondrial membrane potential, increased reactive oxygen species, and apoptotic activities. It was also reported to downregulate mTOR and hTERT gene expression levels which are the primary genes for cell proliferation and growth. This first report on ZOTC combination has the potential to develop as a therapeutic agent for breast cancer.
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Affiliation(s)
- Jayasindu Mathiyazhagan
- School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
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18
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Corradetti B, Vaiasicca S, Mantovani M, Virgili E, Bonucci M, Hammarberg Ferri I. Bioactive Immunomodulatory Compounds: A Novel Combinatorial Strategy for Integrated Medicine in Oncology? BAIC Exposure in Cancer Cells. Integr Cancer Ther 2020; 18:1534735419866908. [PMID: 31416372 PMCID: PMC6699000 DOI: 10.1177/1534735419866908] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The Standardized Cultured Extract of Lentinula edodes Mycelia (also known as
Active Hexose Correlated Compound, AHCC) and Wasabia japonica
(Wasabi) are natural nutritional supplements known for their immunomodulatory
and anticancer potential. The aim of this study was to evaluate the
combinatorial effect of the bioactive immunomodulatory compound (BAIC), obtained
by combining Wasabi and AHCC, on human breast (MCF-7) and pancreatic (Panc02)
adenocarcinoma cell lines. Data obtained revealed that BAIC determines a
striking decline in cancer cell growth at minimal concentrations compared with
the use of Wasabi and AHCC as single agents. A significant increase in the
G0/G1 subpopulation together with a marked
augmentation in the percentage of apoptotic cells was demonstrated by flow
cytometry, together with a significant upregulation in the expression of genes
associated to the apoptotic cascade in both cell lines. The inhibitory role BAIC
plays in mammospheres formation from MCF-7-derived cancer stem cells was shown
with a marked reduction in size and number. Interestingly, when BAIC was exposed
to monocytic cells, no cytotoxic effects were observed. A
monocytes-to-macrophages differentiation was rather observed with the
concomitant acquisition of an anti-inflammatory phenotype. Taken together, our
findings suggest that BAIC could be used as a potential integration of standard
chemotherapy treatments because of the improved inhibitory activity on cancer
cell proliferation and reduced potential adverse effects.
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Affiliation(s)
- Bruna Corradetti
- 1 Università Politecnica delle Marche, Ancona, Italy.,2 Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.,3 Center for Nanohealth, Swansea University Medical School, Swansea, UK
| | | | - Mauro Mantovani
- 4 Associazione Ricerche Terapie Innovative BioIntegrate, Bologna, Italy
| | - Edy Virgili
- 5 Associazione Ricerca Terapie Oncologiche Integrate, Rome, Italy
| | - Massimo Bonucci
- 5 Associazione Ricerca Terapie Oncologiche Integrate, Rome, Italy.,6 "Villa Benedetta" Hospital, Rome, Italy
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Czarnik-Kwaśniak J, Kwaśniak K, Kwasek P, Świerzowska E, Strojewska A, Tabarkiewicz J. The Influence of Lycopene, [6]-Gingerol, and Silymarin on the Apoptosis on U-118MG Glioblastoma Cells In Vitro Model. Nutrients 2019; 12:E96. [PMID: 31905849 PMCID: PMC7019537 DOI: 10.3390/nu12010096] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 12/22/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Lycopene, gingerol, and silymarin have a potential anticancer activity in many types of neoplasms. Healthy lifestyle and proper diet are associated with a reduced risk of cancer and other diseases. Increasingly, clinical research focuses on the mechanisms of action of natural compounds and their impact on the development of cancer. The aim of the present study was to determine the effect of lycopene, gingerol, and silymarin on apoptosis, mitochondrial potential and caspase-3/7 activity in the U118-MG cell line. METHODS Human glioblastoma cells were incubated with lycopene, [6]-gingerol, and silymarin for 24 and 48 h. Apoptosis was monitored using the Annexin V labelling, caspase-3/7 activity, and early hallmark of apoptosis were determined with mitochondrial membrane potential changes. RESULTS Our data showed a significant decrease in the viability glioblastoma cells U118-MG after 48 h treatment with lycopene, [6]-gingerol, and silymarin. CONCLUSIONS Our data could confirm the stimulative effects of used compounds on apoptosis and changes in mitochondrial potential in a dose-dependent manner.
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Affiliation(s)
- Justyna Czarnik-Kwaśniak
- Centre for Innovative Research in Medical and Natural Sciences, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland;
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
| | - Konrad Kwaśniak
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
| | - Paulina Kwasek
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
| | - Elżbieta Świerzowska
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
| | - Agata Strojewska
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
| | - Jacek Tabarkiewicz
- Centre for Innovative Research in Medical and Natural Sciences, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland;
- Department of Human Immunology, Medical Faculty of University of Rzeszow, 1a Warzywna St., 35-310 Rzeszow, Poland; (K.K.); (P.K.); (E.Ś.); (A.S.)
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20
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Nedungadi D, Binoy A, Vinod V, Vanuopadath M, Nair SS, Nair BG, Mishra N. Ginger extract activates caspase independent paraptosis in cancer cells via ER stress, mitochondrial dysfunction, AIF translocation and DNA damage. Nutr Cancer 2019; 73:147-159. [PMID: 31690139 DOI: 10.1080/01635581.2019.1685113] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 10/21/2019] [Accepted: 10/21/2019] [Indexed: 01/01/2023]
Abstract
The rhizome of ginger (Zingiber officinale) a common culinary agent is also known for its medicinal activity. We have earlier reported that pure 6-shogaol, an important component of ginger induces paraptosis in triple negative breast cancer (MDA-MB-231) and non small cell lung (A549) cancer cells. However, the chemopreventive potential of the whole ginger extract in food remains to be elucidated. Here, we demonstrate for the first time that ginger extract (GE) triggers similar anticancer activity/paraptosis against the same cell lines but through different molecular mechanisms. Q-TOF LC-MS analysis of the extract showed the presence of several other metabolites along with 6-shogaol and 6-gingerol. GE induces cytoplasmic vacuolation through ER stress and dilation of the ER. Drastic decrease in the mitochondrial membrane potential and ATP production along with the excess generation of ROS contributed to mitochondrial dysfunction. Consequently, GE caused the translocation of apoptosis inducing factor to the nucleus leading to the fragmentation of DNA. Taken together, these show a novel mechanism for ginger extract induced cancer cell death that can be of potential interest for cancer preventive strategies.
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Affiliation(s)
- Divya Nedungadi
- School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
| | - Anupama Binoy
- School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
| | - Vivek Vinod
- Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, India
| | | | | | - Bipin G Nair
- School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
| | - Nandita Mishra
- School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India
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21
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Lechner JF, Stoner GD. Gingers and Their Purified Components as Cancer Chemopreventative Agents. Molecules 2019; 24:E2859. [PMID: 31394732 PMCID: PMC6719158 DOI: 10.3390/molecules24162859] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 07/29/2019] [Accepted: 08/05/2019] [Indexed: 12/17/2022] Open
Abstract
Chemoprevention by ingested substituents is the process through which nutraceuticals and/or their bioactive components antagonize carcinogenesis. Carcinogenesis is the course of action whereby a normal cell is transformed into a neoplastic cell. This latter action involves several steps, starting with initiation and followed by promotion and progression. Driving these stages is continued oxidative stress and inflammation, which in turn, causes a myriad of aberrant gene expressions and mutations within the transforming cell population and abnormal gene expressions by the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs primarily via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review, we discuss how the chemoprevention activities of gingers antagonize cancer development.
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Affiliation(s)
- John F Lechner
- Retired from Department of Medicine, Division of Medical Oncology, Ohio State University, Columbus 43210, OH, USA.
| | - Gary D Stoner
- Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA
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22
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Shang Y, Wang Q, Wu B, Zhao Q, Li J, Huang X, Chen W, Gui R. Platelet-Membrane-Camouflaged Black Phosphorus Quantum Dots Enhance Anticancer Effect Mediated by Apoptosis and Autophagy. ACS APPLIED MATERIALS & INTERFACES 2019; 11:28254-28266. [PMID: 31291079 DOI: 10.1021/acsami.9b04735] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.
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Affiliation(s)
- Yinghui Shang
- Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
| | - Qinghai Wang
- Department of Cardiology , the Second Hospital of Shandong University , Jinan 250000 , P. R. China
| | - Bin Wu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College , Huazhong University of Science and Technology , Wuhan 430022 , P. R. China
| | - Qiangqiang Zhao
- Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
| | - Jian Li
- Clinical Laboratory of the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
| | - Xueyuan Huang
- Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
| | - Wansong Chen
- College of Chemistry and Chemical Engineering , Central South University , Changsha 410083 , P. R. China
| | - Rong Gui
- Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
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Vemuri SK, Banala RR, Subbaiah G, Srivastava SK, Reddy AG, Malarvili T. Anti-cancer potential of a mix of natural extracts of turmeric, ginger and garlic: A cell-based study. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.ejbas.2017.07.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Satish Kumar Vemuri
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
- Rajah Serfoji Government College, Thanjavur, Tamil Nadu, India
| | - Rajkiran Reddy Banala
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - G.P.V. Subbaiah
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - Saurabh Kumar Srivastava
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - A.V. Gurava Reddy
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
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24
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Hseu YC, Huang YC, Thiyagarajan V, Mathew DC, Lin KY, Chen SC, Liu JY, Hsu LS, Li ML, Yang HL. Anticancer activities of chalcone flavokawain B from Alpinia pricei Hayata in human lung adenocarcinoma (A549) cells via induction of reactive oxygen species-mediated apoptotic and autophagic cell death. J Cell Physiol 2019; 234:17514-17526. [PMID: 30847898 DOI: 10.1002/jcp.28375] [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: 10/23/2018] [Revised: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 12/20/2022]
Abstract
Chalcones found in fruits and vegetables have promising cancer chemopreventive properties. This study attempts to identify the anticancer efficacies of chalcone flavokawain B (FKB) in the rhizomes of Alpinia pricei Hayata by examining key molecular events in non-small-cell lung cancer (A549) cells. Our results indicated that in human A549 cells, FKB (0-15 μg/ml) decreases cell viability and colony formation, dysregulates the Bax:B-cell lymphoma 2 ratio and increases apoptotic DNA fragmentation. Mitochondrial (caspase-9/-3 and poly ADP ribose polymerase [PARP]) signaling was found to be involved in FKB-induced apoptosis. In addition, FKB-induced reactive oxygen species (ROS) generation, and N-acetylcysteine attenuated FKB-induced apoptotic cell death. Moreover, FKB triggered autophagy, as evidenced by the improved acidic vesicular organelle formation, lipidated light chain 3 (microtubule-related light chain 3) accumulation, and ATG7 expression and the decreased mammalian target of rapamycin phosphorylation. Furthermore, FKB suppressed ROS-mediated ATG4B expression. Inhibiting autophagy using 3-methyladenine/chloroquine diminished FKB-induced cell death, indicating that autophagy is triggered as a death mechanism by FKB. In summary, FKB has a crucial role in the execution and propagation of ROS-mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.
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Affiliation(s)
- You-Cheng Hseu
- Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.,Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.,Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.,Research Center of Chinese Herbal Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Chi Huang
- Department of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
| | - Varadharajan Thiyagarajan
- Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
| | - Dony Chacko Mathew
- Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
| | - Kai-Yuan Lin
- Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
| | - Ssu-Ching Chen
- Department of Life Sciences, National Central University, Chung-Li, Taiwan
| | - Jer-Yuh Liu
- Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan
| | - Li-Sung Hsu
- Department of Biomedical Sciences, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
| | - Mei-Ling Li
- Department of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
| | - Hsin-Ling Yang
- Department of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan
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Almatroudi A, Alsahli MA, Alrumaihi F, Allemailem KS, Rahmani AH. Ginger: A Novel Strategy to Battle Cancer through Modulating Cell Signalling Pathways: A Review. Curr Pharm Biotechnol 2019; 20:5-16. [PMID: 30659535 DOI: 10.2174/1389201020666190119142331] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 12/17/2018] [Accepted: 01/07/2019] [Indexed: 12/24/2022]
Abstract
Numerous studies have been performed in understanding the development of cancer. Though, the mechanism of action of genes in the development of cancer remains to be explained. The current mode of treatment of cancer shows adverse effects on normal cells and also alter the cell signalling pathways. However, ginger and its active compound have fascinated research based on animal model and laboratories during the past decade due to its potentiality in killing cancer cells. Ginger is a mixture of various compounds including gingerol, paradol, zingiberene and shogaol and such compounds are the main players in diseases management. Most of the health-promoting effects of ginger and its active compound can be attributed due to its antioxidant and anti-tumour activity. Besides, the active compound of ginger has proven its role in cancer management through its modulatory effect on tumour suppressor genes, cell cycle, apoptosis, transcription factors, angiogenesis and growth factor. In this review, the role of ginger and its active compound in the inhibition of cancer growth through modulating cell signalling pathways will be reviewed and discussed.
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Affiliation(s)
- Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Mohammed A Alsahli
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Faris Alrumaihi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Khaled S Allemailem
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Arshad H Rahmani
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
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de Lima RMT, Dos Reis AC, de Menezes AAPM, Santos JVDO, Filho JWGDO, Ferreira JRDO, de Alencar MVOB, da Mata AMOF, Khan IN, Islam A, Uddin SJ, Ali ES, Islam MT, Tripathi S, Mishra SK, Mubarak MS, Melo-Cavalcante AADC. Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: A comprehensive review. Phytother Res 2018; 32:1885-1907. [PMID: 30009484 DOI: 10.1002/ptr.6134] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 05/31/2018] [Accepted: 06/05/2018] [Indexed: 12/21/2022]
Abstract
Natural dietary agents have attracted considerable attention due to their role in promoting health and reducing the risk of diseases including cancer. Ginger, one of the most ancient known spices, contains bioactive compounds with several health benefits. [6]-Gingerol constitutes the most pharmacologically active among such compounds. The aim of the present work was to review the literature pertaining to the use of ginger extract and [6]-gingerol against tumorigenic and oxidative and inflammatory processes associated with cancer, along with the underlying mechanisms of action involved in signaling pathways. This will shed some light on the protective or therapeutic role of ginger derivatives in oxidative and inflammatory regulations during metabolic disturbance and on the antiproliferative and anticancer properties. Data collected from experimental (in vitro or in vivo) and clinical studies discussed in this review indicate that ginger extract and [6]-gingerol exert their action through important mediators and pathways of cell signaling, including Bax/Bcl2, p38/MAPK, Nrf2, p65/NF-κB, TNF-α, ERK1/2, SAPK/JNK, ROS/NF-κB/COX-2, caspases-3, -9, and p53. This suggests that ginger derivatives, in the form of an extract or isolated compounds, exhibit relevant antiproliferative, antitumor, invasive, and anti-inflammatory activities.
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Affiliation(s)
- Rosália Maria Tôrres de Lima
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - Antonielly Campinho Dos Reis
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - Ag-Anne Pereira Melo de Menezes
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - José Victor de Oliveira Santos
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - José Williams Gomes de Oliveira Filho
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - José Roberto de Oliveira Ferreira
- Laboratory of Experimental Cancerology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - Marcus Vinícius Oliveira Barros de Alencar
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - Ana Maria Oliveira Ferreira da Mata
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
| | - Ishaq N Khan
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
| | - Amirul Islam
- Pharmacy Discipline, School of Life Sciences, Khulna University, Khulna, Bangladesh
| | - Shaikh Jamal Uddin
- Pharmacy Discipline, School of Life Sciences, Khulna University, Khulna, Bangladesh
| | - Eunüs S Ali
- Gaco Pharmaceuticals and Research Laboratory, Dhaka-1000, Bangladesh; College of Medicine and Public Health, Flinders University, Bedford Park, Australia
| | - Muhammad Torequl Islam
- Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam
- Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam
| | - Swati Tripathi
- Amity Institute of Microbial Technology, Amity University, Noida, India
| | - Siddhartha Kumar Mishra
- Cancer Biology Laboratory, School of Biological Sciences (Zoology), Dr. Harisingh Gour Central University, Sagar, India
| | | | - Ana Amélia de Carvalho Melo-Cavalcante
- Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil
- Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil
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Iawsipo P, Srisook E, Ponglikitmongkol M, Somwang T, Singaed O. Cytotoxic effects of Etlingera pavieana
rhizome on various cancer cells and identification of a potential anti-tumor component. J Food Biochem 2018. [DOI: 10.1111/jfbc.12540] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Panata Iawsipo
- Department of Biochemistry, Faculty of Science; Burapha University; Chonburi 20131 Thailand
- Centre of Excellence for Innovation in Chemistry; Burapha University; Chonburi 20131 Thailand
| | - Ekaruth Srisook
- Centre of Excellence for Innovation in Chemistry; Burapha University; Chonburi 20131 Thailand
- Department of Chemistry, Faculty of Science; Burapha University; Chonburi 20131 Thailand
| | | | - Tatiyar Somwang
- Department of Biochemistry, Faculty of Science; Burapha University; Chonburi 20131 Thailand
| | - Onanong Singaed
- Department of Biochemistry, Faculty of Science; Burapha University; Chonburi 20131 Thailand
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Wang F, Sun Y. Overexpression of Myosin Phosphatase Target Subunit 1 (MYPT1) Inhibits Tumor Progression and Metastasis of Gastric Cancer. Med Sci Monit 2018; 24:2508-2517. [PMID: 29687789 PMCID: PMC5937360 DOI: 10.12659/msm.906852] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background Myosin phosphatase target subunit 1 (MYPT1) serves as a subgroup of myosin phosphatases, and is frequently low-expressed in human cancers. However, little is known about the effects of MYPT1 in gastric cancer (GC). Material/Methods In our study, MYPT1 expression was detected by quantitative real-time reverse transcription PCR (qRT-PCR) in GC tissues, different advanced pathological stages of GC tissues, and preoperative and postoperative patients. Kaplan-Meier analysis was used to measure the overall survival of GC patients. MYPT1 expression was analyzed by qRT-PCR and Western blot assays in GES-1 cells and GC cells. Cell proliferation, cycle, and migration and invasion abilities were detected by CCK-8, flow cytometry, and Transwell assays. E-cadherin, TIMP-2, MMP-2, MMP-9 RhoA, and p-RhoA expressions were assessed by qRT-PCR and Western blot assays in treated SNU-5 cells. Results Our results indicated that MYPT1 was down-regulated in GC tissues and cells, and is related to clinical stages and overall survival of GC. Functional research demonstrated that overexpression of MYPT1 can inhibit cell proliferation, cell cycle progression, and migration and invasion of GC cells. Many studies on mechanisms reported that overexpression of MYPT1 dramatically improved the expression levels of cell cycle-related genes (Cyclin D1 and c-myc), significantly increased epithelial marker (E-cadherin) expression, and decreased invasion-associated genes (TIMP-2 and MMP-2) expressions in SNU-5 cells. In addition, we found that MYPT1 suppressed RhoA phosphorylation. Conclusions We verified that MYPT1 inhibits GC cell proliferation and metastasis by regulating RhoA phosphorylation.
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Affiliation(s)
- Fengyong Wang
- Department of Gastrointestinal and Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)
| | - Yuanshui Sun
- Department of Gastrointestinal and Pancreatic Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland)
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Al-Zahrani AA. Saudi anti-human cancer plants database (SACPD): A collection of plants with anti-human cancer activities. Oncol Rev 2018; 12:349. [PMID: 29774137 PMCID: PMC5939832 DOI: 10.4081/oncol.2018.349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 03/01/2018] [Indexed: 01/31/2023] Open
Abstract
Several anticancer drugs have been developed from natural products such as plants. Successful experiments in inhibiting the growth of human cancer cell lines using Saudi plants were published over the last three decades. Up to date, there is no Saudi anticancer plants database as a comprehensive source for the interesting data generated from these experiments. Therefore, there was a need for creating a database to collect, organize, search and retrieve such data. As a result, the current paper describes the generation of the Saudi anti-human cancer plants database (SACPD). The database contains most of the reported information about the naturally growing Saudi anticancer plants. SACPD comprises the scientific and local names of 91 plant species that grow naturally in Saudi Arabia. These species belong to 38 different taxonomic families. In Addition, 18 species that represent16 family of medicinal plants and are intensively sold in the local markets in Saudi Arabia were added to the database. The website provides interesting details, including plant part containing the anticancer bioactive compounds, plants locations and cancer/cell type against which they exhibit their anticancer activity. Our survey revealed that breast, liver and leukemia were the most studied cancer cell lines in Saudi Arabia with percentages of 27%, 19% and 15%, respectively. The current SACPD represents a nucleus around which more development efforts can expand to accommodate all future submissions about new Saudi plant species with anticancer activities. SACPD will provide an excellent starting point for researchers and pharmaceutical companies who are interested in developing new anticancer drugs. SACPD is available online at https://teeqrani1.wixsite.com/sapd
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Affiliation(s)
- Ateeq Ahmed Al-Zahrani
- Biology and Chemistry Department, University College at Al-Qunfudhah, Umm AL-Qura University, Makkah, Saudi Arabia
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Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase-Dependent and p53-Independent Pathway in Breast Cancer Cell Lines. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:1468957. [PMID: 29250124 PMCID: PMC5698829 DOI: 10.1155/2017/1468957] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 10/12/2017] [Indexed: 01/16/2023]
Abstract
Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.
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Boroumand Moghaddam A, Moniri M, Azizi S, Abdul Rahim R, Bin Ariff A, Navaderi M, Mohamad R. Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line. Genes (Basel) 2017; 8:genes8100281. [PMID: 29053567 PMCID: PMC5664131 DOI: 10.3390/genes8100281] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 09/24/2017] [Accepted: 10/06/2017] [Indexed: 11/19/2022] Open
Abstract
Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC50) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G1 phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC25, 98.91% at IC50, and 99.44% at IC75. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti-apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways.
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Affiliation(s)
- Amin Boroumand Moghaddam
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Young Research and Elite Club, Sabzevar Branch, Islamic Azad University, Sabzevar, Iran.
| | - Mona Moniri
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Young Research and Elite Club, Sabzevar Branch, Islamic Azad University, Sabzevar, Iran.
| | - Susan Azizi
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Raha Abdul Rahim
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Arbakariya Bin Ariff
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Bioprocessing and Biomanufacturing Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Mohammad Navaderi
- Young Research and Elite Club, Parand Branch, Islamic Azad University, Parand, Iran.
| | - Rosfarizan Mohamad
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
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Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells. Bioorg Med Chem Lett 2017; 27:4389-4392. [PMID: 28835347 DOI: 10.1016/j.bmcl.2017.08.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 08/08/2017] [Accepted: 08/10/2017] [Indexed: 11/23/2022]
Abstract
Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner.
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Dietary Natural Products for Prevention and Treatment of Breast Cancer. Nutrients 2017; 9:nu9070728. [PMID: 28698459 PMCID: PMC5537842 DOI: 10.3390/nu9070728] [Citation(s) in RCA: 173] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/30/2017] [Accepted: 06/30/2017] [Indexed: 02/07/2023] Open
Abstract
Breast cancer is the most common cancer among females worldwide. Several epidemiological studies suggested the inverse correlation between the intake of vegetables and fruits and the incidence of breast cancer. Substantial experimental studies indicated that many dietary natural products could affect the development and progression of breast cancer, such as soy, pomegranate, mangosteen, citrus fruits, apple, grape, mango, cruciferous vegetables, ginger, garlic, black cumin, edible macro-fungi, and cereals. Their anti-breast cancer effects involve various mechanisms of action, such as downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis of breast tumor cells, inducing apoptosis and cell cycle arrest, and sensitizing breast tumor cells to radiotherapy and chemotherapy. This review summarizes the potential role of dietary natural products and their major bioactive components in prevention and treatment of breast cancer, and special attention was paid to the mechanisms of action.
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10-Gingerol as an inducer of apoptosis through HTR1A in cumulus cells: In-vitro and in-silico studies. J Taibah Univ Med Sci 2017; 12:397-406. [PMID: 31435270 PMCID: PMC6695051 DOI: 10.1016/j.jtumed.2017.05.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/17/2017] [Accepted: 05/21/2017] [Indexed: 12/20/2022] Open
Abstract
Objectives Cumulus cells play a crucial role as essential mediators in the maturation of ova. Ginger contains 10-gingerol, which induces apoptosis in colon cancer cells. Based on this hypothesis, this study aimed to determine whether 10-gingerol is able to induce apoptosis in normal cells, namely, cumulus cells. Methods This study used an in vitro analysis by culturing Cumulus cells in M199 containing 10-gingerol in various concentrations (12, 16, and 20 μM) and later detected early apoptotic activity using an Annexin V-FITC detection kit. Result The in vitro data revealed that the number of apoptosis cells increased along with the period of incubation as follows: 12 μM (63.71% ± 2.192%); 16 μM (74.51% ± 4.596%); and 20 μM (78.795% ± 1.435%). The substance 10-gingerol induces apoptosis in cumulus cells by inhibiting HTR1A functions and inactivating GSK3B and AKT-1. Conclusions These findings indicate that further examination is warranted for 10-gingerol as a contraception agent.
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Key Words
- 10-Gingerol
- ARG, arginine
- Apoptosis
- Cumulus cells
- FOXO, forkhead box
- GLU, glutamine
- GLY, glycine
- GSK3B, glycogen synthase kinase-3β
- HTR1A
- HTR1A, 5-hydroxytryptamine receptor 1 A
- ILE, ileusine
- ILK, integrin-linked kinase
- In silico
- In vitro
- LYS, lysine
- MDM2, murine double minute clone 2
- MET, methionine
- NO, nitric oxide
- NOS3, nitric oxide synthase 3
- PTEN, phosphatase and tensin homologue delete on chromosome ten
- RICTOR, rapamycin-insensitive companion of mTOR
- TYR, tyrosine
- eNOS, endothelial nitric oxide synthase
- mTOR, mammalian target of rapamycin
- mTORC1, mTOR complex 1
- mTORC2, mTOR complex 2
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Khazaei S, Esa NM, Ramachandran V, Hamid RA, Pandurangan AK, Etemad A, Ismail P. In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells. Front Pharmacol 2017; 8:5. [PMID: 28197098 PMCID: PMC5281556 DOI: 10.3389/fphar.2017.00005] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Accepted: 01/04/2017] [Indexed: 01/18/2023] Open
Abstract
Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract of A. atroviolaceum was found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated to Cdk1 downregulation, S phase arrest in MDA-MB-231 which is p53 and Cdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned with Cdk1 downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2. Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb of A. atroviolaceum may be useful for the treatment of cancer lonely or in combination with other drugs.
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Affiliation(s)
- Somayeh Khazaei
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | - Norhaizan M Esa
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | | | - Roslida A Hamid
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | - Ashok K Pandurangan
- Department of pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Ali Etemad
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | - Patimah Ismail
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
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Lee DH, Kim SS, Seong S. A Case Report of Metastatic Breast Cancer Treated with Korean Medicine Therapy as a Substitute for Chemotherapy. Case Rep Oncol 2017; 10:27-36. [PMID: 28461813 PMCID: PMC5396200 DOI: 10.1159/000455039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 12/09/2016] [Indexed: 12/02/2022] Open
Abstract
The purpose of this case report is to show the potential benefit of Korean medicine therapy for treating multiple metastatic breast cancer. A 45-year-old Korean woman was diagnosed with right breast invasive ductal carcinoma in August 2012 but did not receive any treatment until October 2015 when she was diagnosed with stage 4 right breast cancer with multiple liver, bone, mesentery, retroperitoneum, and axillary lymph node metastases. After chemo-port insertion, she was treated with palliative chemotherapy and the first line of trastuzumab and paclitaxel, and the port was removed due to port infection. To treat sepsis, vancomycin and tazoperan were administered, before the third line of trastuzumab and paclitaxel was carried out. However, the patient gave up chemotherapy due to vancomycin-resistant enterococci and general weakness. Later, she received Korean medicine therapy with wild ginseng pharmacopuncture, distilled Soramdan S, Hae, and Jeobgoldan for 8 months, which led to a significant decrease of the multiple metastases. The patient was able to start walking again with the help of a walking stick. However, a new metastatic lesion was found on the right adrenal gland. This case suggests that the combination of chemotherapy and Korean medicine therapy may be valuable. Further research is indicated.
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Affiliation(s)
- Dong-Hyun Lee
- Soram Korean Medicine Hospital, Seoul, Republic of Korea
| | - Sung-Su Kim
- Soram Korean Medicine Hospital, Seoul, Republic of Korea
| | - Shin Seong
- Soram Korean Medicine Hospital, Seoul, Republic of Korea
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Hasebe T, Matsukawa J, Ringus D, Miyoshi J, Hart J, Kaneko A, Yamamoto M, Kono T, Fujiya M, Kohgo Y, Wang CZ, Yuan CS, Bissonnette M, Musch MW, Chang EB. Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APC min/+ Mouse Models of Experimental Colon Cancer. Phytother Res 2017; 31:90-99. [PMID: 27730672 PMCID: PMC5590753 DOI: 10.1002/ptr.5735] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/26/2016] [Accepted: 09/18/2016] [Indexed: 02/06/2023]
Abstract
Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Takumu Hasebe
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Jun Matsukawa
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
| | - Daina Ringus
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
| | - Jun Miyoshi
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
| | - John Hart
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Atsushi Kaneko
- Tsumura Research Laboratories, Tsumura and Co., Ami, Ibaraki, Japan
| | | | - Toru Kono
- Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Hokkaido, Japan
- Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yutaka Kohgo
- Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Chong-Zi Wang
- Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA
| | - Marc Bissonnette
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
| | - Mark W. Musch
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
| | - Eugene B. Chang
- Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, IL, USA
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Subramani R, Lakshmanaswamy R. Complementary and Alternative Medicine and Breast Cancer. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2017; 151:231-274. [DOI: 10.1016/bs.pmbts.2017.07.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Ahmed SI, Hayat MQ, Tahir M, Mansoor Q, Ismail M, Keck K, Bates RB. Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. Altern Ther Health Med 2016; 16:460. [PMID: 27835979 PMCID: PMC5106795 DOI: 10.1186/s12906-016-1443-z] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 10/26/2016] [Indexed: 11/10/2022]
Abstract
BACKGROUND Cassia angustifolia Vahl. (commonly known as senna makkai or cassia senna), native to Saudi Arabia, Egypt, Yemen and also extensively cultivated in Pakistan, is a medicinal herb used traditionally to cure number of diseases like liver diseases, constipation, typhoid, cholera etc. This study was conducted to evaluate the in-vitro antimicrobial, antioxidant and anticancer assays and phytochemical constituents of aqueous and organic extracts of C. angustifolia leaves. METHODS The antimicrobial activities of C. angustifolia aqueous and organic (methanol, ethanol, acetone, ethyl acetate) extracts were investigated by the disk diffusion method. These extracts were further evaluated for antioxidant potential by the DPPH radical scavenging assay. Anticancer activities of the extracts were determined by the MTT colorimetric assay. The total phenolic and flavonoid contents of C. angustifolia extracts were evaluated by the Folin-Ciocalteu method and aluminum chloride colorimetric assay, respectively. The structures of the bioactive compounds were elucidated by NMR and ESI-MS spectrometry. RESULTS Bioactivity-guided screening of C. angustifolia extracts, led to the isolation and identification of three flavonoids quercimeritrin (1), scutellarein (2), and rutin (3) reported for the first time from this plant, showed significant anticancer activity against MCF-7 (IC50, 4.0 μg/μL), HeLa (IC50, 5.45 μg/μL), Hep2 (IC50, 7.28 μg/μL) and low cytotoxicity against HCEC (IC50, 21.09 μg/μL). Significant antioxidant activity was observed with IC50 2.41 μg/mL against DPPH radical. Moreover, C. angustifolia extracts have the potential to inhibit microbial growth of E. cloacae, P. aeruginosa, S. mercescens and S. typhi. CONCLUSION C. angustifolia extracts revealed the presence of quercimeritrin (1), scutellarein (2), and rutin (3), all known to have useful bioactivities including antimicrobial, antioxidant and anticancer activities.
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Thomford NE, Mkhize B, Dzobo K, Mpye K, Rowe A, Parker MI, Wonkam A, Skelton M, September AV, Dandara C. African Lettuce (Launaea taraxacifolia) Displays Possible Anticancer Effects and Herb-Drug Interaction Potential by CYP1A2, CYP2C9, and CYP2C19 Inhibition. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2016; 20:528-37. [PMID: 27631192 DOI: 10.1089/omi.2016.0117] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Medicinal plants are part of the healthcare systems worldwide, especially in low- and middle-income countries. African lettuce (Launaea taraxacifolia) is cultivated extensively in Africa, from Senegal in the west to Ethiopia and Tanzania in the east, and in Southern Africa. Potential anticancer effects of L. taraxacifolia have been suggested, but little is known about putative molecular mechanisms or potential for herb-drug interactions through inhibition or induction of drug-metabolizing enzymes. We investigated the effects of crude aqueous extracts of L. taraxacifolia on growth kinetics and cell cycle progression of the WHC01 esophageal cancer cells. Antiproliferative and apoptotic effects were evaluated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and flow cytometry, while examining, in parallel, the genes regulating apoptosis and cell cycle in this cell culture model. In addition, we tested the inhibitory and enzyme kinetic effects of the aqueous L. taraxacifolia using recombinant human CYP450 isozyme model systems (CYP1A2, CYP2C9, and CYP2C19). L. taraxacifolia exhibited a significant growth inhibitory effect on the WHC01 cancer cells. Most cell cycle genes were downregulated. Cell cycle analysis showed a G0-G1 cell cycle arrest in WHC01 cells in the presence of L. taraxacifolia extract, accompanied by morphological changes. L. taraxacifolia extract treatment resulted in downregulation of expression levels of CYP1A2 (p < 0.0005) and CYP2C19 (p < 0.003) by 50-70%. L. taraxacifolia extract caused reversible and time-dependent inhibition of the recombinant CYP1A2, CYP2C9, and CYP2C19. This study provides new insights on possible anticancer effects of L. taraxacifolia, a widely used medicinal plant in parts of Africa and across the world especially by patients with cancer. Further mechanistic studies expanding on these observations would be timely and contribute to the field of global precision medicine that requires solid understanding of drug and herb molecular mechanisms of action and drug-herb interaction potentials, given the worldwide use of medicinal plants.
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Affiliation(s)
- Nicholas E Thomford
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
- 2 School of Medical Sciences, University of Cape Coast , Cape Coast, Ghana
| | - Buyisile Mkhize
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Kevin Dzobo
- 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa
- 4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Keleabetswe Mpye
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Arielle Rowe
- 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa
- 4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - M Iqbal Parker
- 3 International Centre for Genetic Engineering and Biotechnology (ICGEB) , Cape Town, South Africa
- 4 Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Ambroise Wonkam
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Michelle Skelton
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Alison V September
- 5 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
| | - Collet Dandara
- 1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology and Institute of Infectious Diseases and Molecular medicine, Faculty of Health Sciences, University of Cape Town , Cape Town, South Africa
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Annamalai G, Kathiresan S, Kannappan N. [6]-Shogaol, a dietary phenolic compound, induces oxidative stress mediated mitochondrial dependant apoptosis through activation of proapoptotic factors in Hep-2 cells. Biomed Pharmacother 2016; 82:226-36. [PMID: 27470359 DOI: 10.1016/j.biopha.2016.04.044] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 04/22/2016] [Accepted: 04/22/2016] [Indexed: 12/14/2022] Open
Abstract
Ginger (Zingiber officinale) is a well-known herb used in ethnomedicine. [6]-shogaol, a phenolic nature is a major constituent of ginger. In this study, we investigated the anticancer activity of [6]-shogaol in Laryngeal cancer (Hep-2) cells. We demonstrated the effects of [6]-shogaol on the cell growth and apoptosis in Hep-2 cells were analyzed by the generation of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔYm), DNA damage and apoptotic morphological changes were analyzed by AO/EtBr, AO and Hoechst staining. Further, apoptotic protein expressions were analyzed by western blot analysis. Our results indicated that [6]-shogaol induces apoptosis as evidenced by loss of cell viability, enhanced ROS, lipid peroxidation results in altered mitochondrial membrane potential, increased DNA damage in Hep-2 cells. Further, the prooxidant role of [6]-shogaol inhibit Bcl-2 expression with the simultaneous up-regulation of Bax, Cytochrome c, Caspase-9 and -3 protein expressions were observed in Hep-2 cells. Thus, [6]-shogaol induces apoptosis in Hep-2 cells through inducing oxidative damage and modulate apoptotic marker expressions. Therefore, [6]-shogaol might be used as a therapeutic agent for the treatment of laryngeal cancer.
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Affiliation(s)
- Govindhan Annamalai
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India
| | - Suresh Kathiresan
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India.
| | - Nagappan Kannappan
- Department of Pharmacy, Annnamalai University, Annamalainagar, Tamil Nadu, India
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Production of polyunsaturated single cell oils possessing antimicrobial and anticancer properties. ANN MICROBIOL 2015. [DOI: 10.1007/s13213-015-1176-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
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Yim NH, Kim A, Jung YP, Kim T, Ma CJ, Ma JY. Fermented So-Cheong-Ryong-Tang (FCY) induces apoptosis via the activation of caspases and the regulation of MAPK signaling pathways in cancer cells. Altern Ther Health Med 2015; 15:336. [PMID: 26403976 PMCID: PMC4582731 DOI: 10.1186/s12906-015-0821-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 08/13/2015] [Indexed: 12/15/2022]
Abstract
Background So-Cheong-Ryong-Tang (CY), a traditional herbal formula, mainly has been shown to possess allergic rhinitis and asthma for hundreds of years in Asian countries. Although this medicine has been attracted Asian scientists with investigating mechanisms of action against inflammatory-related diseases, there is a little available information on the anti-cancer effect of CY, especially on the fermented form (FCY). In this study, we explored the chemopreventive/chemotherapeutic efficacy of FCY against cancer cells and proved the efficacy of FCY through performing in vivo xenograft assay. Methods CY was fermented with bacteria and lyophilized. For analysis of the constituents of CY and FCY, high performance liquid chromatography (HPLC)-DAD system was performed. To detect the anti-cancer effect of FCY, cell viability assay, caspase activity assay, cell cycle analysis, and Western blot analysis were performed in AGS human gastric cancer cells. The inhibitory effects of tumor growth by CY and FCY were evaluated in athymic nude mice inoculated with HCT116 human colon cancer cells. Results As a result of analyzing the 11components present in CY and FCY, the contents of ephedrine HCl, glycyrrhizin, gingerol, schisandrin, and gomisin A were respectively increased by fermentation in FCY. The treatment of CY or FCY inhibited the viability of AGS cells, interestingly, the inhibition of cancer cell growth was enhanced by fermentation of CY. FCY induced the apoptosis through activating the caspase-3, −8, and −9. Additionally, FCY regulated the activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK). In vivo xenografts, administration of FCY significantly inhibited the tumor formation, and improved the anti-tumor effect compared to that of CY in athymic nude mice. Conclusions FCY indicated significant anti-cancer effects, and its efficacy against tumor formation was improved than that of CY, therefore, FCY might be used for applications of traditional medicine against cancer in modern complementary and alternative therapeutics.
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