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Qaed E, Liu W, Almoiliqy M, Mohamed R, Tang Z. Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3321-3343. [PMID: 39549063 DOI: 10.1007/s00210-024-03579-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 10/28/2024] [Indexed: 11/18/2024]
Abstract
Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Genistein (Gen), a phytoestrogen soy isoflavone, has emerged as a promising agent in the prevention and treatment of breast cancer due to its ability to function as a natural selective estrogen receptor modulator (SERM). This review explores the multifaceted mechanisms through which Gen and its derivatives exert their anticancer effects, including modulation of the PI3K/Akt signaling pathway, regulation of apoptosis, inhibition of angiogenesis, and impacts on DNA methylation and enzyme functions. We discuss the dual roles of Gen in both enhancing and inhibiting estrogen receptor (ER)-dependent pathways., highlighting its complex interactions with ERα and ERβ. Furthermore, the review examines the synergistic effect of combining Gen with conventional chemotherapeutic agents such as doxorubicin, cisplatin, and selenium, as well as other natural compounds like lycopene. Clinical studies suggest that while isoflavones may not significantly influence breast cancer progression in general, the high consumption of soy isoflavones is associated with reduced recurrence rates in breast cancer survivors. Importantly, Gen's ability to modulate key signaling pathways and enhance the efficacy of existing treatments improves its potential as a valuable adjunct in breast cancer therapy. In conclusion, Gen and its derivatives offer a novel and promising approach for treatment of breast cancer. Continued research into their mechanisms of action and clinical applications will be essential in optimizing their therapeutic potential and translating these findings into effective clinical interventions.
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Affiliation(s)
- Eskandar Qaed
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China.
- State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
| | - Wu Liu
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China
| | - Marwan Almoiliqy
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China
| | - Rawan Mohamed
- College of Clinical Pharmacy, Mansoura University, Mansoura, Egypt
| | - Zeyao Tang
- Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, 9 West Section, South Road of Lushun Dalian, Dalian, 116044, China.
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2
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Tu SN, Hu F, Zhang J, Cai H, Yang J. Research progress on the signaling pathway mechanism of terpenoids against breast cancer. Discov Oncol 2025; 16:433. [PMID: 40163255 PMCID: PMC11958888 DOI: 10.1007/s12672-025-01881-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/03/2025] [Indexed: 04/02/2025] Open
Abstract
Breast cancer is the most common malignant tumor in women worldwide. Current treatments include chemotherapy, hormone therapy, radiotherapy and surgery. Terpenoids have great anti-cancer potential due to their anti-inflammatory, antioxidant, anti-tumor, antiviral and other biological activities. They have become the central drug for the prevention and treatment of breast cancer. However, their low bioavailability and stability are urgent issues that need to be addressed. This article aims to sort out the mechanism of action of terpenoids in the treatment of breast cancer. By reviewing different signal transduction pathways, it is hoped that new ideas for the joint action of multiple pathways and multiple targets will be provided, and a theoretical basis will be provided for improving basic research and clinical treatment of breast cancer.
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Affiliation(s)
- Sheng-Nan Tu
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, 063210, China
| | - Fen Hu
- College of Life Sciences, North China University of Science and Technology, Tangshan, 063210, China
| | - Juan Zhang
- Second Department of Mammary Gland, Tangshan People's Hospital, Tangshan, 063000, China
| | - Haifeng Cai
- Second Department of Mammary Gland, Tangshan People's Hospital, Tangshan, 063000, China.
| | - Junquan Yang
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, 063210, China.
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3
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Rai N, Kailashiya V, Gautam V. Exploring the Protective Effect against 7,12-Dimethylbenz[a]anthracene-Induced Breast Tumors of Palmitoylethanolamide. ACS Pharmacol Transl Sci 2024; 7:97-109. [PMID: 38230286 PMCID: PMC10789129 DOI: 10.1021/acsptsci.3c00188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/26/2023] [Accepted: 10/31/2023] [Indexed: 01/18/2024]
Abstract
Breast cancer remains a global health burden, and the need for effective therapies is of chief importance. The current study explored the in vivo chemoprotective activity of palmitoylethanolamide (PEA) against 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast tumor in rats. Results of noninvasive photoacoustic imaging showed real-time progression in the tumor area and volume in DMBA-induced rats, while there was a reduction in tumor area and volume in PEA-treated tumor-bearing rats. The increase in the average oxygen saturation (sO2 %) and decrease in the average total hemoglobin (HbT %) indicated the PEA-mediated attenuation of hypoxia-induced neovascularization in DMBA-induced rats. Histopathological investigations confirmed the efficacy of PEA in mitigating breast carcinoma, hepatotoxicity and nephrotoxicity driven by DMBA. Moreover, PEA-mediated alterations in the metabolic activity of the tumor microenvironment were evidenced by decreased glucose and lactate dehydrogenase enzyme level in the blood plasma and mammary tissue. PEA also maintained the redox balance by inhibiting nitric oxide level, reducing malondialdehyde (a product of lipid peroxidation), and increasing the level of antioxidant enzyme reduced glutathione. PEA altered the expression of apoptosis-related genes (BAX, P53,BCL-XL, CASPASE-8, and CASPASE-9) and induced the activity of Caspase-3 protein in the mammary tissue of tumor-bearing rats, indicating its apoptosis inducing ability. Taken together, the findings of this study suggest that PEA may have a protective effect against DMBA-induced breast tumors.
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Affiliation(s)
- Nilesh Rai
- Centre
of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
| | - Vikas Kailashiya
- Department
of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
| | - Vibhav Gautam
- Centre
of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
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Islam F, Khan J, Zehravi M, Das R, Haque MA, Banu A, Parwaiz S, Nainu F, Nafady MH, Shahriar SMS, Hossain MJ, Muzammil K, Emran TB. Synergistic effects of carotenoids: Therapeutic benefits on human health. Process Biochem 2024; 136:254-272. [DOI: 10.1016/j.procbio.2023.11.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies. Nutrients 2022; 14:nu14235152. [PMID: 36501182 PMCID: PMC9741066 DOI: 10.3390/nu14235152] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/25/2022] [Accepted: 11/29/2022] [Indexed: 12/10/2022] Open
Abstract
Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.
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Hsu HY, Chen BH. A Comparative Study on Inhibition of Breast Cancer Cells and Tumors in Mice by Carotenoid Extract and Nanoemulsion Prepared from Sweet Potato ( Ipomoea batatas L.) Peel. Pharmaceutics 2022; 14:980. [PMID: 35631566 PMCID: PMC9144854 DOI: 10.3390/pharmaceutics14050980] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 11/16/2022] Open
Abstract
The objectives of this study were to determine carotenoid composition in sweet potato (TNG66) peel and prepare carotenoid nanoemulsion to study its inhibition effect on breast cancer cells MCF-7 and tumors in mice. Results showed that a total of 10 carotenoids were separated within 30 min by employing a YMC C30 column and a gradient mobile phase of methanol/acetonitrile/water (74:14:12, v/v/v) and dichloromethane (B) with a flow rate of 1 mL/min, column temperature of 25 °C, and detection wavelength of 450 nm. Following quantitation, all-trans-β-carotene was present in the highest amount (663.8 μg/g). The method validation data demonstrated a high accuracy and precision of this method. The carotenoid nanoemulsion was prepared by mixing an appropriate proportion of carotenoid extract, Tween 80, PEG 400, soybean oil and deionized water with the mean particle size being 15.7 nm (transmission electron microscope (TEM)), polydispersity index 0.238, encapsulation efficiency 97% and zeta potential -69.8 mV. A high stability of carotenoid nanoemulsion was shown over a 90-day storage period at 25 °C and during heating at 100 °C for 2 h. The release percentage of total carotenoids from carotenoid nanoemulsion under gastric and intestinal condition was 18.3% and 49.1%, respectively. An antiproliferation study revealed that carotenoid nanoemulsion was more effective than carotenoid extract in inhibiting the growth of human breast cancer cells MCF-7. Following treatments of paclitaxel (10 μg/mL), carotenoid nanoemulsion (20 and 10 μg/mL) and carotenoid extract (20 and 10 μg/mL), the tumor weight of mice respectively decreased by 77.4, 56.2, 40.3, 36.1 and 18.7%, as well as tumor volume of mice by 75.4, 65.0, 49.7, 46.7 and 26.5%. Also, both carotenoid extract and nanoemulsion could reduce the levels of epidermal growth factor (EGF) and (vascular endothelial growth factor (VEGF) in serum, with the latter being more effective. This finding suggested that carotenoid nanoemulsion was more effective than carotenoid extract in inhibiting tumor growth in mice.
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Affiliation(s)
- Hsin-Yen Hsu
- Department of Food Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan;
| | - Bing-Huei Chen
- Department of Food Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan;
- Department of Nutrition, China Medical University, Taichung 40402, Taiwan
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7
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Genistein, a Potential Phytochemical against Breast Cancer Treatment-Insight into the Molecular Mechanisms. Processes (Basel) 2022. [DOI: 10.3390/pr10020415] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer side effects on normal cells. Therefore, we aimed to unravel and analyze several molecular mechanisms of genistein (GNT) against BC. GNT is a type of dietary phytoestrogen included in the flavonoid group with a similar structure to estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutic drugs. Previous research reported that GNT could target the estrogen receptor (ER) human epidermal growth factor receptor-2 (HER2) and several signaling molecules against multiple BC cell lines and sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. More specifically, GNT mediates the anticancer mechanism through apoptosis induction, arresting the cell cycle, inhibiting angiogenesis and metastasis, mammosphere formation, and targeting and suppressing tumor growth factors. Furthermore, it acts via upregulating tumor suppressor genes and downregulating oncogenes in vitro and animal model studies. In addition, this phytochemical synergistically reverses the resistance mechanism of standard chemotherapeutic drugs, increasing their efficacy against BC. Overall, in this review, we discuss several molecular interactions of GNT with numerous cellular targets in the BC model and show its anticancer activities alone and synergistically. We conclude that GNT can have favorable therapeutic advantages when standard drugs are not available in the pharma markets.
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Ke DYJ, El-Sahli S, Wang L. The Potential of Natural Products in the Treatment of Triple-Negative Breast Cancer. Curr Cancer Drug Targets 2021; 22:388-403. [PMID: 34970954 DOI: 10.2174/1568009622666211231140623] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 11/01/2021] [Accepted: 11/09/2021] [Indexed: 11/22/2022]
Abstract
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks receptors for targeted therapy. Consequently, chemotherapy is currently the mainstay of systemic treatment options. However, the enrichment of cancer stem cells (CSC, a subpopulation with stem-cell characteristics and tumor-initiating propensity) promotes chemo-resistance and tumorigenesis, resulting in cancer recurrence and relapse. Furthermore, toxic side effects of chemotherapeutics reduce patient wellbeing. Natural products, specifically compounds derived from plants, have the potential to treat TNBC and target CSCs by inhibiting CSC signaling pathways. Literature evidence from six promising compounds were reviewed, including sulforaphane, curcumin, genistein, resveratrol, lycopene, and epigallocatechin-3-gallate. These compounds have been shown to promote cell cycle arrest and apoptosis in TNBC cells. They also could inhibit the epithelial-mesenchymal transition (EMT) that plays an important role in metastasis. In addition, those natural compounds have been found to inhibit pathways important for CSCs, such as NF-κB, PI3K/Akt/mTOR, Notch 1, Wnt/β-catenin, and YAP. Clinicals trials conducted on these compounds have shown varying degrees of effectiveness. Epidemiological case-control studies for the compounds commonly consumed in certain human populations have also been summarized. While in vivo and in vitro data are promising, further basic and clinical investigations are required. Likely, natural products in combination with other drugs may hold great potential to improve TNBC treatment efficacy and patient outcomes.
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Affiliation(s)
- Danny Yu Jia Ke
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Ottawa, Canada
- Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
- The Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
| | - Sara El-Sahli
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Ottawa, Canada
- Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
- The Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
| | - Lisheng Wang
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Ottawa, Canada
- Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
- The Centre for Infection, Immunity and Inflammation (CI3), University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada
- Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
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9
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Kubczak M, Szustka A, Rogalińska M. Molecular Targets of Natural Compounds with Anti-Cancer Properties. Int J Mol Sci 2021; 22:ijms222413659. [PMID: 34948455 PMCID: PMC8708931 DOI: 10.3390/ijms222413659] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer is the second leading cause of death in humans. Despite rapid developments in diagnostic methods and therapies, metastasis and resistance to administrated drugs are the main obstacles to successful treatment. Therefore, the main challenge should be the diagnosis and design of optimal therapeutic strategies for patients to increase their chances of responding positively to treatment and increase their life expectancy. In many types of cancer, a deregulation of multiple pathways has been found. This includes disturbances in cellular metabolism, cell cycle, apoptosis, angiogenesis, or epigenetic modifications. Additionally, signals received from the microenvironment may significantly contribute to cancer development. Chemical agents obtained from natural sources seem to be very attractive alternatives to synthetic compounds. They can exhibit similar anti-cancer potential, usually with reduced side effects. It was reported that natural compounds obtained from fruits and vegetables, e.g., polyphenols, flavonoids, stilbenes, carotenoids and acetogenins, might be effective against cancer cells in vitro and in vivo. Several published results indicate the activity of natural compounds on protein expression by its influence on transcription factors. They could also be involved in alterations in cellular response, cell signaling and epigenetic modifications. Such natural components could be used in our diet for anti-cancer protection. In this review, the activities of natural compounds, including anti-cancer properties, are described. The influence of natural agents on cancer cell metabolism, proliferation, signal transduction and epigenetic modifications is highlighted.
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Affiliation(s)
- Małgorzata Kubczak
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Aleksandra Szustka
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
| | - Małgorzata Rogalińska
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-237 Łódź, Poland;
- Correspondence:
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10
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Alhoshani A, Alotaibi M, As Sobeai HM, Alharbi N, Alhazzani K, Al-Dhfyan A, Alanazi FE, Korashy HM. In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis. Saudi J Biol Sci 2021; 28:7396-7403. [PMID: 34867043 PMCID: PMC8626299 DOI: 10.1016/j.sjbs.2021.08.051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/12/2021] [Accepted: 08/15/2021] [Indexed: 01/02/2023] Open
Abstract
Metformin (MET) is a clinically used anti-hyperglycemic agent that shows activities against chemically-induced animal models of cancer. A study from our laboratory showed that MET protectes against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in vitro human non-cancerous epithelial breast cells (MCF10A) via activation of the aryl hydrocarbon receptor (AhR). However, it is unclear whether MET can prevent the initiation of breast carcinogenesis in an in vivo rat model of AhR-induced breast carcinogenesis. Therefore, the main aims of this study are to examine the effect of MET on protecting against rat breast carcinogenesis induced by DMBA and to explore whether this effect is medicated through the AhR pathway. In this study, treatment of female rats with DMBA initiated breast carcinogenesis though inhibiting apoptosis and tumor suppressor genes while inducing oxidative DNA damage and cell cycle proliferative markers. This effect was associated with activation of AhR and its downstream target genes; cytochrome P4501A1 (CYP1A1) and CYP1B1. Importantly, MET treatment protected against DMBA-induced breast carcinogenesis by restoring DMBA effects on apoptosis, tumor suppressor genes, DNA damage, and cell proliferation. Mechanistically using in vitro human breast cancer MCF-7 cells, MET inhibited breast cancer stem cells spheroids formation and development by DMBA, which was accompanied by a proportional inhibition in CYP1A1 gene expression. In conclusion, the study reports evidence that MET is an effective chemopreventive therapy for breast cancer by inhibiting the activation of CYP1A1/CYP1B1 pathway in vivo rat model.
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Affiliation(s)
- Ali Alhoshani
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Moureq Alotaibi
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Homood M As Sobeai
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Naif Alharbi
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Khalid Alhazzani
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Abdullah Al-Dhfyan
- Stem Cell & Tissue Re-Engineering, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
| | - Fawaz E Alanazi
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Hesham M Korashy
- Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
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11
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Kumar G, Du B, Chen J. Effects and mechanisms of dietary bioactive compounds on breast cancer prevention. Pharmacol Res 2021; 178:105974. [PMID: 34818569 DOI: 10.1016/j.phrs.2021.105974] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/05/2021] [Accepted: 11/06/2021] [Indexed: 12/17/2022]
Abstract
Breast cancer (BC) is the most often diagnosed cancer among females globally and has become an increasing global health issue over the last decades. Despite the substantial improvement in screening methods for initial diagnosis, effective therapy remains lacking. Still, there has been high recurrence and disease progression after treatment of surgery, endocrine therapy, chemotherapy, and radiotherapy. Considering this view, there is a crucial requirement to develop safe, freely accessible, and effective anticancer therapy for BC. The dietary bioactive compounds as auspicious anticancer agents have been recognized to be active and their implications in the treatment of BC with negligible side effects. Hence, this review focused on various dietary bioactive compounds as potential therapeutic agents in the prevention and treatment of BC with the mechanisms of action. Bioactive compounds have chemo-preventive properties as they inhibit the proliferation of cancer cells, downregulate the expression of estrogen receptors, and cell cycle arrest by inducing apoptotic settings in tumor cells. Therapeutic drugs or natural compounds generally incorporate engineered nanoparticles with ideal sizes, shapes, and enhance their solubility, circulatory half-life, and biodistribution. All data of in vitro, in vivo, and clinical studies of dietary bioactive compounds and their impact on BC were collected from Science Direct, PubMed, and Google Scholar. The data of chemopreventive and anticancer activity of dietary bioactive compounds were collected and orchestrated in a suitable place in the review. These shreds of data will be extremely beneficial to recognize a series of additional diet-derived bioactive compounds to treat BC with the lowest side effects.
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Affiliation(s)
- Ganesan Kumar
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Bing Du
- College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510640, China
| | - Jianping Chen
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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12
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Simkin AJ. Carotenoids and Apocarotenoids in Planta: Their Role in Plant Development, Contribution to the Flavour and Aroma of Fruits and Flowers, and Their Nutraceutical Benefits. PLANTS (BASEL, SWITZERLAND) 2021; 10:plants10112321. [PMID: 34834683 PMCID: PMC8624010 DOI: 10.3390/plants10112321] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 05/05/2023]
Abstract
Carotenoids and apocarotenoids are diverse classes of compounds found in nature and are important natural pigments, nutraceuticals and flavour/aroma molecules. Improving the quality of crops is important for providing micronutrients to remote communities where dietary variation is often limited. Carotenoids have also been shown to have a significant impact on a number of human diseases, improving the survival rates of some cancers and slowing the progression of neurological illnesses. Furthermore, carotenoid-derived compounds can impact the flavour and aroma of crops and vegetables and are the origin of important developmental, as well as plant resistance compounds required for defence. In this review, we discuss the current research being undertaken to increase carotenoid content in plants and research the benefits to human health and the role of carotenoid derived volatiles on flavour and aroma of fruits and vegetables.
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Affiliation(s)
- Andrew J. Simkin
- School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK; or
- Crop Science and Production Systems, NIAB-EMR, New Road, East Malling, Kent ME19 6BJ, UK
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13
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Kim JA, Jang JH, Lee SY. An Updated Comprehensive Review on Vitamin A and Carotenoids in Breast Cancer: Mechanisms, Genetics, Assessment, Current Evidence, and Future Clinical Implications. Nutrients 2021; 13:3162. [PMID: 34579037 PMCID: PMC8465379 DOI: 10.3390/nu13093162] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/28/2021] [Accepted: 09/06/2021] [Indexed: 12/11/2022] Open
Abstract
Vitamin A and carotenoids are fat-soluble micronutrients that play important role as powerful antioxidants modulating oxidative stress and cancer development. Breast cancer is the most common malignancy in women. As the risk of breast cancer is dependent on various lifestyle factors such as dietary modifications, there is increasing interest surrounding the anti-cancerous properties of vitamin A and carotenoids. Despite the suggested protective roles of vitamin A and carotenoids in breast cancer development, their clinical application for the prevention and treatment of breast cancer is limited. In this narrative review, we discuss the roles of vitamin A and carotenoids along with the evaluation method of vitamin A status. We also exhibit the association of genetic variations involved in metabolism of vitamin A and carotenoids with cancers and other diseases. We demonstrate the epidemiological evidence for the relationship of vitamin A and carotenoids with breast cancer risk, their effects on cancer mechanism, and the recent updates in clinical practice of vitamin A or carotenoids as a potential therapeutic agent against breast cancer. This review provides insight into the preventive and therapeutic roles of vitamin A and carotenoids in breast cancer development and progression.
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Affiliation(s)
- Jee Ah Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.A.K.); (J.-H.J.)
| | - Ja-Hyun Jang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.A.K.); (J.-H.J.)
| | - Soo-Youn Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; (J.A.K.); (J.-H.J.)
- Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
- Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, 115 Irwon-ro, Gangnam-gu, Seoul 06355, Korea
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14
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Song X, Luo Y, Ma L, Hu X, Simal-Gandara J, Wang LS, Bajpai VK, Xiao J, Chen F. Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent. Semin Cancer Biol 2021; 73:331-346. [PMID: 33794344 DOI: 10.1016/j.semcancer.2021.03.028] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 02/07/2023]
Abstract
Dietary interventions are key nutritional strategies to prevent, improve, and prolong the survival of cancer patients. Lycopene, one of the strongest natural antioxidants, and its biologically active metabolites, have shown significant potential to prevent a variety of cancers, including prostate, breast, and stomach cancers, making it a promising anti-cancer agent. We review the potential regulatory mechanisms and epidemiological evidences of lycopene and its metabolites to delay the progression of cancers at different developmental stages. Recent studies have revealed that lycopene and its metabolites mediate multiple molecular mechanisms in cancer treatment such as redox homeostasis, selective anti-proliferation, apoptosis, anti-angiogenesis, tumour microenvironment regulation, and anti-metastasis and anti-invasion. Gut microbes and cholesterol metabolism are also the potential regulation targets of lycopene and its metabolites. As a dietary supplement, the synergistic interaction of lycopene with other drugs and nutrients is highlighted especially due to its binding activity with other nutrients in the diet found central to the fight against cancer. Furthermore, the application of several of novel lycopene delivery carriers are on the rise including nanoemulsions, nanostructured liposomes, and polymer nanoparticles for cancer prevention as discussed in this review with future needed development. Moreover, the synergistic mechanism between lycopene and other nutrients or drugs and novel delivery systems of lycopene should now be deeply investigated to improve its clinical application in cancer intervention in the future.
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Affiliation(s)
- Xunyu Song
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Yinghua Luo
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Lingjun Ma
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Xiaosong Hu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China
| | - Jesus Simal-Gandara
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain
| | - Li-Shu Wang
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Vivek K Bajpai
- Department of Energy and Materials Engineering, Dongguk University, 30 Pildong-ro 1-gil, Seoul 04620, Republic of Korea
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain.
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, China.
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15
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Upreti S, Pandey SC, Bisht I, Samant M. Evaluation of the target-specific therapeutic potential of herbal compounds for the treatment of cancer. Mol Divers 2021; 26:1823-1835. [PMID: 34240331 DOI: 10.1007/s11030-021-10271-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 07/02/2021] [Indexed: 11/25/2022]
Abstract
Cancer is among one of the most fatal diseases leading to millions of death around the globe. Chemotherapy is the most popular conventional approach for the treatment of cancer. However, this is usually associated with various side effects and puts the patients under extreme physical and mental stress. Besides, there are increasing concerns about drug resistance. Thus, to surmount these limitations, there is a need to explore some alternative treatments. Studies related to plant-derived compounds are crucial in the search for safer and more efficient treatments. Plants and their associated secondary metabolites have been a revolutionary approach in the field of cancer treatment, as they give answers to almost all the constraints faced by synthetic drugs. Various plants and associated secondary metabolites display a great prospective as cytotoxic anticancer agents due to their specific interference with validated drug targets, such as inhibitors of mitosis, topoisomerase I and II inhibitor, DNA interactive agent, protein kinase inhibitors, inhibitors of DNA synthesis. In this review, the therapeutic potential of various natural compounds and their derivatives are presented based on their molecular targets. These herbal compounds and their derivatives could provide a rich resource for novel anticancer drug development.
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Affiliation(s)
- Shobha Upreti
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Satish Chandra Pandey
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Ila Bisht
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Mukesh Samant
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India.
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16
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Chopra B, Dhingra AK. Natural products: A lead for drug discovery and development. Phytother Res 2021; 35:4660-4702. [PMID: 33847440 DOI: 10.1002/ptr.7099] [Citation(s) in RCA: 182] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 03/01/2021] [Accepted: 03/09/2021] [Indexed: 12/29/2022]
Abstract
Natural products are used since ancient times in folklore for the treatment of various ailments. Plant-derived products have been recognized for many years as a source of therapeutic agents and structural diversity. A literature survey has been carried out to determine the utility of natural molecules and their modified analogs or derivatives as pharmacological active entities. This review presents a study on the importance of natural products in terms of drug discovery and development. It describes how the natural components can be utilized after small modifications in new perspectives. Various new modifications in structure offer a unique opportunity to establish a new molecular entity with better pharmacological potential. It was concluded that in this current era, new attempts are taken to utilize the compounds derived from natural sources as novel drug candidates, with a focus to find and discover new effective molecules that were referred to as "new entities of natural product drug discovery."
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Affiliation(s)
- Bhawna Chopra
- Department of Pharmaceutical Chemistry, Guru Gobind Singh College of Pharmacy, Yamuna Nagar, India
| | - Ashwani Kumar Dhingra
- Department of Pharmaceutical Chemistry, Guru Gobind Singh College of Pharmacy, Yamuna Nagar, India
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17
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Suleiman RB, Muhammad A, Umara IA, Ibrahima MA, Erukainure OL, Forcados GE, Katsayal SB. Kolaviron Ameliorates 7, 12-Dimethylbenzanthracene - Induced Mammary Damage in Female Wistar Rats. Anticancer Agents Med Chem 2021; 22:181-192. [PMID: 34225638 DOI: 10.2174/1871520621666210322101232] [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: 08/10/2020] [Revised: 12/27/2020] [Accepted: 01/25/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Kolaviron (KV) is a flavonoid rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders. OBJECTIVE To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats. METHODS Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100 and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice in a week and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanly sacrificed and ER-α, sialic acids, sialidase, sialyltransferase levels were assay for in blood and mammary tissues followed by histopathological examinations. RESULTS Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100 and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, significantly (p<0.05) lower free serum sialic acid (21.1%), total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions. CONCLUSION The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.
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Affiliation(s)
- Rabiatu B Suleiman
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Ismaila A Umara
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Mohammed A Ibrahima
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Ochuko L Erukainure
- Department of Pharmacology, University of the Free State, Bloemfontein 9300. South Africa
| | - Gilead E Forcados
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Sanusi B Katsayal
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
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18
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AKTEPE OH, ŞAHİN TK, GÜNER G, ARIK Z, YALÇIN Ş. Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway. Turk J Med Sci 2021; 51:368-374. [PMID: 32718121 PMCID: PMC7991865 DOI: 10.3906/sag-2005-413] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/21/2020] [Indexed: 12/24/2022] Open
Abstract
Background/aim Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. Materials and methods HeLa cells were treated with cisplatin (1 μM) alone, lycopene (10 μM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-κB), B-cell-associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2). Results We found that lycopene acts as a synergistic agent with cisplatin in preventing the growth of HeLa cells. The rates of HeLa cells’ viability were 65.6% and 71.1% with lycopene and cisplatin treatment alone compared to the control group, respectively (P < 0.001). The inhibitory effect of cisplatin was enhanced with lycopene addition by declining the cell viability to 37.4% (P < 0.0001). Lycopene treatment significantly increased Bax expression (P < 0.0001) and decreased Bcl-2 expression (P < 0.0001) in HeLa cells. Furthermore, lycopene markedly activated the Nrf2 expression (P < 0.001) and suppressed the NF-κB signaling pathway (P < 0.0001). Conclusion Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, the anticancer effect of lycopene might be also associated with suppression of NF-κB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer.
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Affiliation(s)
- Oktay Halit AKTEPE
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Taha Koray ŞAHİN
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Gürkan GÜNER
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Zafer ARIK
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Şuayib YALÇIN
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
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19
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Wise LA, Wesselink AK, Bethea TN, Brasky TM, Wegienka G, Harmon Q, Block T, Baird DD. Intake of Lycopene and other Carotenoids and Incidence of Uterine Leiomyomata: A Prospective Ultrasound Study. J Acad Nutr Diet 2021; 121:92-104. [PMID: 33350944 PMCID: PMC7768815 DOI: 10.1016/j.jand.2020.08.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/23/2020] [Accepted: 08/12/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene was associated with reduced size and incidence of oviduct leiomyoma in the Japanese quail. Two US prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. OBJECTIVE This study examines the association between dietary intake of carotenoids and UL incidence. DESIGN Data were derived from the Study of the Environment, Lifestyle, and Fibroids, a prospective cohort study. Women completed self-administered baseline questionnaires on demographic characteristics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids-including alpha carotene, beta carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene-and vitamin A were estimated. PARTICIPANTS/SETTING One thousand two hundred thirty Black women aged 23 to 35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease were eligible for enrollment (2010-2012). Participants were residents of the Detroit, MI, metropolitan area. MAIN OUTCOME MEASURES Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. STATISTICAL ANALYSES PERFORMED Cox regression was used to estimate hazard ratios and 95% CIs, adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. RESULTS Among 1,230 women without prevalent UL at baseline, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. Hazard ratios comparing quartiles 2 (2,376 to 3,397 μg/day), 3 (3,398 to 4,817 μg/day), and 4 (≥4,818 μg/day) with quartile 1 (<2,376 μg/day) of lycopene intake were 1.03 (95% CI 0.72 to 1.47), 1.22 (95% CI 0.86 to 1.72), and 0.95 (95% CI 0.67 to 1.36), respectively. CONCLUSIONS Study findings do not support the hypothesis that greater carotenoid intake is associated with reduced UL incidence.
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Affiliation(s)
- Lauren A Wise
- (1)Department of Epidemiology, Boston University School of Public Health, Boston, MA.
| | - Amelia K Wesselink
- (1)Department of Epidemiology, Boston University School of Public Health, Boston, MA
| | - Traci N Bethea
- (2)Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC
| | - Theodore M Brasky
- (3)Division of Medical Oncology, The Ohio State University College of Medicine; Columbus, OH
| | - Ganesa Wegienka
- (4)Department of Public Health Sciences, Henry Ford Health System; Detroit, MI
| | - Quaker Harmon
- (5)Epidemiology Branch, Women's Health Group, National Institute for Environmental Health Sciences, Research Triangle, NC
| | | | - Donna D Baird
- (5)Epidemiology Branch, Women's Health Group, National Institute for Environmental Health Sciences, Research Triangle, NC
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20
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Forcados GE, Sallau AB, Muhammad A, Erukainure OL, James DB. Vitex doniana Leaves Extract Ameliorates Alterations Associated with 7, 12-Dimethyl Benz[a]Anthracene-Induced Mammary Damage in Female Wistar Rats. Nutr Cancer 2020; 73:98-112. [PMID: 32223342 DOI: 10.1080/01635581.2020.1743866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Vitex doniana leaves are used traditionally in West Africa for the treatment of swellings and cancer. We investigated if Vitex doniana leaves extract could ameliorate 7, 12-dimethylbenz[a]anthracene (DMBA)-induced mammary damage. Female Wistar rats aged 52 ± 2 day were administered 80 mg/kg DMBA. After monitoring for 150 day, rats were administered 0, 50, 100, 200 mg/kg Vitex doniana and 20 mg/kg Tamoxifen for 14 day. Serum estrogen receptor-α, IL-1β and TNF -α levels were determined using ELISA kits. Oxidative stress markers in mammary tissue homogenates were determined using standard spectrophotometric methods. Histopathological examination was done using hematoxylin and eosin staining and cyclooxygenase-2 (COX-2) expression using immunohistochemistry. Liquid chromatography-mass spectrometry was used to determine components present in the extract. Although tumors were not observed, significantly (p < 0.05) lower estrogen receptor-α, malondialdehyde, IL-1β and TNF -α levels, significantly (p < 0.05) higher glutathione and catalase activity, attenuation of malignant epithelial hyperplasia and mild COX-2 expression were observed in rats administered Vitex doniana when compared to DMBA-induced untreated control. Liquid chromatography-mass spectrometry analysis of the V. doniana extract revealed the presence of 4,5-dihydroxy-7-methoxy-6-methylflavone and vanillylamine, which are compounds with reported antioxidant and anti-inflammatory effects. Collectively, treatment with Vitex doniana ameliorated some derangement observed in DMBA-induced rats.
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Affiliation(s)
| | | | - Aliyu Muhammad
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - Ochuko Lucky Erukainure
- Nutrition and Toxicology Division, Federal Institute of Industrial Research, Oshodi, Lagos, Nigeria.,Department of Pharmacology, University of the Free State, Bloemfontein, South Africa
| | - Dorcas Bolanle James
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria
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21
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Sahin K, Yabas M, Orhan C, Tuzcu M, Sahin TK, Ozercan IH, Qazi S, Uckun FM. Prevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinases. Expert Opin Ther Targets 2020; 24:379-387. [PMID: 32106727 DOI: 10.1080/14728222.2020.1737014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Objectives: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer model.Methods: One hundred BALB/cmice were divided into five groups. (i) Control (ii) DMBA (iii) DMBA+ Paclitaxel (10 mg/kg) (iv) DMBA+WHI-P131 (Janex1, 50 mg/kg of BW, i.p, three times per week) ("J") (v) DMBA+P+J. The duration of study was 25 weeks.Results: Our findings demonstrate that WHI-P131 impedes DMBA-induced carcinogenesis, reduces size, weight, and load of tumors (P < 0.001) in DMBA-challenged mice and improves their survival outcome (P < 0.01). The tumors developing despite WHI-P131 chemoprevention displayedattenuated levels of JAK3, STAT3, and NF-κB as well as increased I-κB expression (P < 0.001). Notably, these tumors exhibited significantly decreased levels of phosphorylated AKT-PI3-Kinase pathway signaling proteins p-mTOR, p-p70S6K1, and p-4E-BP1 (P < 0.001). Our findings are consistent with a model in which DMBA-induced malignant clones with low-level expression of the six signature proteins JAK3/STAT3/NF-κB/p-mTOR, p-p70S6K1/p-4E-BP1, albeit not as aggressive as their JAK3/STAT3/NF-κB overexpressing counterparts are capable of escaping chemo-preventive effects of WHI-P131.Conclusion: These insights may provide the foundation for new chemo-preventive strategies in which WHI-P131 is applied to prevent the development of aggressive forms of breast cancer.
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Affiliation(s)
- Kazim Sahin
- Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Mehmet Yabas
- Department of Genetics and Bioengineering, Trakya University, Edirne, Turkey
| | - Cemal Orhan
- Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Mehmet Tuzcu
- Department of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Taha K Sahin
- Department of Internal Medicine, University of Hacettepe School of Medicine, Ankara, Turkey
| | - Ibrahim H Ozercan
- Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Sanjive Qazi
- Division of Hematology-Oncology, Department of Pediatrics and Developmental Therapeutics Program, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA.,Department of Immuno-Oncology, Ares Pharmaceuticals, St. Paul, MN, USA
| | - Fatih M Uckun
- Division of Hematology-Oncology, Department of Pediatrics and Developmental Therapeutics Program, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA.,Department of Immuno-Oncology, Ares Pharmaceuticals, St. Paul, MN, USA
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22
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Sahin K, Orhan C, Ozercan IH, Tuzcu M, Elibol B, Sahin TK, Kilic U, Qazi S, Uckun FM. Chemopreventive efficacy of stampidine in a murine breast cancer model. Expert Opin Ther Targets 2020; 24:155-162. [PMID: 32005098 DOI: 10.1080/14728222.2020.1724961] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Background: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model.Methods: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks.Results: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2.Conclusion: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
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Affiliation(s)
- Kazim Sahin
- Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Cemal Orhan
- Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | | | - Mehmet Tuzcu
- Department of Molecular Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Birsen Elibol
- Department of Medical Biology, University of Bezmialem, School of Medicine, Istanbul, Turkey
| | - Taha Koray Sahin
- Department of Internal Medicine, University of Hacettepe School of Medicine, Ankara, Turkey
| | - Ulkan Kilic
- Department of Medical Biology, University of Health Sciences, School of Medicine, Istanbul, Turkey
| | - Sanjive Qazi
- Division of Hematology-Oncology, Department of Pediatrics, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA.,Department of Immuno-Oncology, Ares Pharmaceuticals, St. Paul, MN, USA.,Gustavus Adolphus College, St. Peter, MN, USA
| | - Fatih Mehmet Uckun
- Division of Hematology-Oncology, Department of Pediatrics, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA.,Department of Immuno-Oncology, Ares Pharmaceuticals, St. Paul, MN, USA
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23
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Ma JK, Saad Eldin WF, El-Ghareeb WR, Elhelaly AE, Khedr MHE, Li X, Huang XC. Effects of Pyrene on Human Liver HepG2 Cells: Cytotoxicity, Oxidative Stress, and Transcriptomic Changes in Xenobiotic Metabolizing Enzymes and Inflammatory Markers with Protection Trial Using Lycopene. BIOMED RESEARCH INTERNATIONAL 2019; 2019:7604851. [PMID: 31687396 PMCID: PMC6803749 DOI: 10.1155/2019/7604851] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 09/11/2019] [Accepted: 09/20/2019] [Indexed: 01/05/2023]
Abstract
Pyrene is one of the major polycyclic aromatic hydrocarbons formed during heat treatment of meat and in car exhausts; however, few studies have investigated pyrene-induced adverse effects on human cell lines. This study aimed at the investigation of pyrene-induced cytotoxicity and oxidative damage in human liver HepG2 cells at environmentally relevant concentrations. Pyrene-induced changes in mRNA expression of xenobiotic metabolizing enzymes (XMEs), xenobiotic transporters, antioxidant enzymes, and inflammatory markers were investigated using real-time PCR. As a protection trial, the ameliorative effects of lycopene, a carotenoid abundantly found in tomato, were investigated. The possible mechanisms behind such effects were examined via studying the co exposure effects of pyrene and lycopene on regulatory elements including the aryl hydrocarbon receptor (Air) and elytroid 2-related factor 2 (RF). The achieved results indicated that pyrene caused significant cytotoxicity at 50 n, with a clear production of reactive oxygen species (ROS) in a dose-dependent manner. Pyrene upregulated mRNA expression of phase I enzymes including CYP1A1, 1A2, and CYP1B1 and inflammatory markers including TNFα and Cox2. However, pyrene significantly downregulated phase II enzymes, xenobiotic transporters, and antioxidant enzymes. Interestingly, lycopene significantly reduced pyrene-induced cytotoxicity and ROS production. Moreover, lycopene upregulated detoxification and antioxidant enzymes, probably via its regulatory effects on Air- and RF-dependent pathways.
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Affiliation(s)
- Jin-Kui Ma
- School of Food & Pharmaceutical Engineering, Zhaoqing University, Zhaoqing 526061, China
| | - Walaa Fathy Saad Eldin
- Educational Veterinary Hospital, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Waleed Rizk El-Ghareeb
- Department of Veterinary Public Health and Animal Husbandry, College of Veterinary Medicine, King Faisal University, Al Hofuf, Saudi Arabia
| | - Abdelazim Elsayed Elhelaly
- Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
- Center for Emerging Infectious Diseases, School of Medicine, Gifu University, Gifu 501-1193, Japan
| | - Mariam H. E. Khedr
- Department of Veterinary Hygiene, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Xiang Li
- College of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing 526061, China
| | - Xiao-Chen Huang
- School of Food & Pharmaceutical Engineering, Zhaoqing University, Zhaoqing 526061, China
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Moorehead RA. Rodent Models Assessing Mammary Tumor Prevention by Soy or Soy Isoflavones. Genes (Basel) 2019; 10:E566. [PMID: 31357528 PMCID: PMC6722900 DOI: 10.3390/genes10080566] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/26/2019] [Accepted: 07/09/2019] [Indexed: 12/14/2022] Open
Abstract
While epidemiological studies performed in Asian countries generally show that high levels of dietary soy are associated with reduced breast cancer risk, studies in Western countries have typically failed to show this correlation. In an attempt to model the preventative actions of soy on mammary tumor development, rodent models have been employed. Thirty-four studies were identified that evaluated the impact of soy products or purified soy isoflavones on mammary tumor initiation (studies evaluating established mammary tumors or mammary tumor cell lines were not included) and these studies were separated into mammary tumors induced by chemical carcinogens or transgenic expression of oncogenes based on the timing of soy administration. Regardless of when soy-based diets or purified isoflavones were administered, no consistent protective effects were observed in either carcinogen-induced or oncogene-induced mammary tumors. While some studies demonstrated that soy or purified isoflavones could reduce mammary tumor incidence, other studies showed either no effect or tumor promoting effects of soy products or isoflavones. Most importantly, only five studies found a decrease in mammary tumor incidence and six studies observed a decrease in tumor multiplicity, two relevant measures of the tumor preventative effects of soy or isoflavones. The variable outcomes of the studies examined were not completely surprising given that few studies employed the same experimental design. Future studies should be carefully designed to more accurately emulate soy consumption observed in Asian cultures including lifetime exposure to less refined soy products and potentially the incorporation of multigenerational feeding studies.
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Affiliation(s)
- Roger A Moorehead
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1, Canada.
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25
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Chinnadhurai M, Al-Otaibi F, Nelson K, Kandasamy G, Shanmugam M, Venkatnarayanan R. Protective Effect of Madhuca longifolia Leaves in 7, 12-Dimethylbenz(a)anthracene Induced Mammary Carcinoma in Sprague Dawley Rat model. Pharmacogn Mag 2019. [DOI: 10.4103/pm.pm_7_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Grabowska M, Wawrzyniak D, Rolle K, Chomczyński P, Oziewicz S, Jurga S, Barciszewski J. Let food be your medicine: nutraceutical properties of lycopene. Food Funct 2019; 10:3090-3102. [DOI: 10.1039/c9fo00580c] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In this review, we highlight research and clinical trials involving lycopene and its impact on human health.
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Affiliation(s)
- Małgorzata Grabowska
- Institute of Bioorganic Chemistry of the Polish Academy of Sciences
- 61-704 Poznan
- Poland
| | - Dariusz Wawrzyniak
- Institute of Bioorganic Chemistry of the Polish Academy of Sciences
- 61-704 Poznan
- Poland
| | - Katarzyna Rolle
- Institute of Bioorganic Chemistry of the Polish Academy of Sciences
- 61-704 Poznan
- Poland
- Centre for Advanced Technology
- Adam Mickiewicz University
| | | | | | - Stefan Jurga
- NanoBioMedical Centre
- Adam Mickiewicz University
- 61-614 Poznan
- Poland
| | - Jan Barciszewski
- Institute of Bioorganic Chemistry of the Polish Academy of Sciences
- 61-704 Poznan
- Poland
- NanoBioMedical Centre
- Adam Mickiewicz University
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Sahin K, Tuzcu M, Yabas M, Orhan C, Sahin N, Ozercan IH. LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice. Invest New Drugs 2018; 36:388-395. [PMID: 29139009 DOI: 10.1007/s10637-017-0540-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 11/09/2017] [Indexed: 10/18/2022]
Abstract
The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.
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Affiliation(s)
- Kazim Sahin
- Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.
| | - Mehmet Tuzcu
- Department of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Mehmet Yabas
- Department of Genetics and Bioengineering, Trakya University, Edirne, Turkey
| | - Cemal Orhan
- Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Nurhan Sahin
- Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Ibrahim H Ozercan
- Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey
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Sahin K, Yenice E, Tuzcu M, Orhan C, Mizrak C, Ozercan IH, Sahin N, Yilmaz B, Bilir B, Ozpolat B, Kucuk O. Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens. J Cancer Prev 2018; 23:25-36. [PMID: 29629346 PMCID: PMC5886492 DOI: 10.15430/jcp.2018.23.1.25] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/09/2018] [Accepted: 03/09/2018] [Indexed: 12/16/2022] Open
Abstract
Background Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.
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Affiliation(s)
- Kazim Sahin
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | | | - Mehmet Tuzcu
- Division of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Cemal Orhan
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | | | - Ibrahim H Ozercan
- Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Nurhan Sahin
- Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey
| | - Bahiddin Yilmaz
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Birdal Bilir
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Bulent Ozpolat
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Omer Kucuk
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
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Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol 2017; 174:1290-1324. [PMID: 27638711 PMCID: PMC5429337 DOI: 10.1111/bph.13625] [Citation(s) in RCA: 439] [Impact Index Per Article: 54.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 08/21/2016] [Accepted: 08/31/2016] [Indexed: 01/06/2023] Open
Abstract
Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Alireza Milani
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
| | | | - Sepideh Shahbazi
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
| | - Azam Bolhassani
- Department of Hepatitis and AIDSPasteur Institute of IranTehranIran
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Wang Z, Zhang X. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats. Front Pharmacol 2017; 8:320. [PMID: 28620301 PMCID: PMC5450001 DOI: 10.3389/fphar.2017.00320] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 05/15/2017] [Indexed: 12/30/2022] Open
Abstract
Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA)-induced mammary cancer in female Sprague Dawlely (SD) rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg) through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p.) were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.
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Affiliation(s)
- Zhenyu Wang
- Department of Breast Surgery, The Second Hospital of Jilin UniversityChangchun, China
| | - Xingyi Zhang
- Department of Thoracic Surgery, The Second Hospital of Jilin UniversityChangchun, China
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Abd-Ellatef GEF, Ahmed OM, Abdel-Reheim ES, Abdel-Hamid AHZ. Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation. BREAST CANCER (DOVE MEDICAL PRESS) 2017; 9:67-83. [PMID: 28280387 PMCID: PMC5340250 DOI: 10.2147/bctt.s125165] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. METHODS Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. RESULTS Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. CONCLUSION In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system.
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Affiliation(s)
- Gamal-Eldein F Abd-Ellatef
- Pharmaceutical and Drug Industries Research Division, Therapeutic Chemistry Department, National Research Centre, Cairo, Egypt
| | - Osama M Ahmed
- Division of Physiology, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Eman S Abdel-Reheim
- Division of Physiology, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Abdel-Hamid Z Abdel-Hamid
- Pharmaceutical and Drug Industries Research Division, Therapeutic Chemistry Department, National Research Centre, Cairo, Egypt
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Alvarado A, Faustino-Rocha AI, Colaço B, Oliveira PA. Experimental mammary carcinogenesis - Rat models. Life Sci 2017; 173:116-134. [PMID: 28188729 DOI: 10.1016/j.lfs.2017.02.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/26/2017] [Accepted: 02/06/2017] [Indexed: 12/22/2022]
Abstract
Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.
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Affiliation(s)
- Antonieta Alvarado
- Área de Patología, Decanato de Ciencias Veterinarias, Universidad Centroccidental "Lisandro Alvarado", UCLA, Lara, Venezuela; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal
| | - Ana I Faustino-Rocha
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal
| | - Bruno Colaço
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Department of Zootechnics, School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal
| | - Paula A Oliveira
- Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, UTAD, Vila Real, Portugal.
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Falah RR, Talib WH, Shbailat SJ. Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis. Ther Adv Med Oncol 2017; 9:235-252. [PMID: 28491145 PMCID: PMC5405996 DOI: 10.1177/1758834016687482] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 12/12/2016] [Indexed: 12/19/2022] Open
Abstract
Background: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. Materials and methods: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c mice with EMT6/P cells and examining tumor growth and apoptosis induction in tumor sections. Furthermore, serum levels of different cytokines and transaminases and creatinine were measured to detect the immune response and toxicity, respectively. Results: The combination treatment exhibited the highest effects against tumor proliferation and growth. It significantly reduced VEGF expression, induced Trp53 independent apoptosis, triggered Th2 immune response and showed no toxicity. Conclusion: The combination can be a potential therapeutic option to treat breast cancer. However, further testing is needed to measure the exact serum levels of MET and CUR and to further explain the obtained results.
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Affiliation(s)
- Rabah Rashad Falah
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman, Jordan
| | - Wamidh H Talib
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman, 11931-166, Jordan
| | - Seba Jamal Shbailat
- Department of Biology and Biotechnology, The Hashemite University, Zarqa, Jordan
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Dietz BM, Hajirahimkhan A, Dunlap TL, Bolton JL. Botanicals and Their Bioactive Phytochemicals for Women's Health. Pharmacol Rev 2016; 68:1026-1073. [PMID: 27677719 PMCID: PMC5050441 DOI: 10.1124/pr.115.010843] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Botanical dietary supplements are increasingly popular for women's health, particularly for older women. The specific botanicals women take vary as a function of age. Younger women will use botanicals for urinary tract infections, especially Vaccinium macrocarpon (cranberry), where there is evidence for efficacy. Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Some examples include Vitex agnus-castus (chasteberry), Angelica sinensis (dong quai), Viburnum opulus/prunifolium (cramp bark and black haw), and Zingiber officinale (ginger). Pregnant women have also used ginger for relief from nausea. Natural galactagogues for lactating women include Trigonella foenum-graecum (fenugreek) and Silybum marianum (milk thistle); however, rigorous safety and efficacy studies are lacking. Older women suffering menopausal symptoms are increasingly likely to use botanicals, especially since the Women's Health Initiative showed an increased risk for breast cancer associated with traditional hormone therapy. Serotonergic mechanisms similar to antidepressants have been proposed for Actaea/Cimicifuga racemosa (black cohosh) and Valeriana officinalis (valerian). Plant extracts with estrogenic activities for menopausal symptom relief include Glycine max (soy), Trifolium pratense (red clover), Pueraria lobata (kudzu), Humulus lupulus (hops), Glycyrrhiza species (licorice), Rheum rhaponticum (rhubarb), Vitex agnus-castus (chasteberry), Linum usitatissimum (flaxseed), Epimedium species (herba Epimedii, horny goat weed), and Medicago sativa (alfalfa). Some of the estrogenic botanicals have also been shown to have protective effects against osteoporosis. Several of these botanicals could have additional breast cancer preventive effects linked to hormonal, chemical, inflammatory, and/or epigenetic pathways. Finally, although botanicals are perceived as natural safe remedies, it is important for women and their healthcare providers to realize that they have not been rigorously tested for potential toxic effects and/or drug/botanical interactions. Understanding the mechanism of action of these supplements used for women's health will ultimately lead to standardized botanical products with higher efficacy, safety, and chemopreventive properties.
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Affiliation(s)
- Birgit M Dietz
- University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois
| | - Atieh Hajirahimkhan
- University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois
| | - Tareisha L Dunlap
- University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois
| | - Judy L Bolton
- University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois
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Bae JK, Kim YJ, Chae HS, Kim DY, Choi HS, Chin YW, Choi YH. Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition. Xenobiotica 2016; 47:450-459. [PMID: 27189791 DOI: 10.1080/00498254.2016.1182233] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models. 2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone. 3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions.
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Affiliation(s)
- Jin Kyung Bae
- a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea
| | - You-Jin Kim
- a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea
| | - Hee-Sung Chae
- a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea
| | - Do Yeun Kim
- b Department of Internal Medicine , Dongguk University, Ilsan Hospital , Goyang , Republic of Korea , and
| | - Han Seok Choi
- c Division of Endocrinology and Metabolism , Department of Internal Medicine, Dongguk University Ilsan Hospital , Koyang , Republic of Korea
| | - Young-Won Chin
- a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea
| | - Young Hee Choi
- a BK21 PLUS R-FIND Team and College of Pharmacy, Dongguk University-Seoul , Goyang , Republic of Korea
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Bak MJ, Das Gupta S, Wahler J, Suh N. Role of dietary bioactive natural products in estrogen receptor-positive breast cancer. Semin Cancer Biol 2016; 40-41:170-191. [PMID: 27016037 DOI: 10.1016/j.semcancer.2016.03.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 03/16/2016] [Accepted: 03/20/2016] [Indexed: 12/20/2022]
Abstract
Estrogen receptor (ER)-positive breast cancer, including luminal-A and -B, is the most common type of breast cancer. Extended exposure to estrogen is associated with an increased risk of breast cancer. Both ER-dependent and ER-independent mechanisms have been implicated in estrogen-mediated carcinogenesis. The ER-dependent pathway involves cell growth and proliferation triggered by the binding of estrogen to the ER. The ER-independent mechanisms depend on the metabolism of estrogen to generate genotoxic metabolites, free radicals and reactive oxygen species to induce breast cancer. A better understanding of the mechanisms that drive ER-positive breast cancer will help optimize targeted approaches to prevent or treat breast cancer. A growing emphasis is being placed on alternative medicine and dietary approaches toward the prevention and treatment of breast cancer. Many natural products and bioactive compounds found in foods have been shown to inhibit breast carcinogenesis via inhibition of estrogen induced oxidative stress as well as ER signaling. This review summarizes the role of bioactive natural products that are involved in the prevention and treatment of estrogen-related and ER-positive breast cancer.
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Affiliation(s)
- Min Ji Bak
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
| | - Soumyasri Das Gupta
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
| | - Joseph Wahler
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
| | - Nanjoo Suh
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
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Naciff JM, Khambatta ZS, Carr GJ, Tiesman JP, Singleton DW, Khan SA, Daston GP. Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein. Toxicol Sci 2016; 151:71-87. [PMID: 26865667 DOI: 10.1093/toxsci/kfw024] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action.
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Affiliation(s)
- Jorge M Naciff
- *Mason Business Center, The Procter and Gamble Company, Mason, Ohio 45040
| | - Zubin S Khambatta
- *Mason Business Center, The Procter and Gamble Company, Mason, Ohio 45040
| | - Gregory J Carr
- *Mason Business Center, The Procter and Gamble Company, Mason, Ohio 45040
| | - Jay P Tiesman
- *Mason Business Center, The Procter and Gamble Company, Mason, Ohio 45040
| | - David W Singleton
- Department of Cell Biology, Neurobiology, and Anatomy, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, Ohio 45267
| | - Sohaib A Khan
- Department of Cell Biology, Neurobiology, and Anatomy, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, Ohio 45267
| | - George P Daston
- *Mason Business Center, The Procter and Gamble Company, Mason, Ohio 45040
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Han Y, Wu J, Liu T, Hu Y, Zheng Q, Wang B, Lin H, Li X. Separation, characterization and anticancer activities of a sulfated polysaccharide from Undaria pinnatifida. Int J Biol Macromol 2016; 83:42-9. [PMID: 26616455 DOI: 10.1016/j.ijbiomac.2015.11.049] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/10/2015] [Accepted: 11/18/2015] [Indexed: 01/13/2023]
Abstract
The purpose of this paper was to investigate separation, characterization and anticancer activities of a sulfated polysaccharide (SPUP) from Undaria pinnatifida. Firstly, polysaccharide from U. pinnatifida was separated by DEAE-52 cellulose and Sephacryl S-400 column chromatography. As results, SPUP was obtained with the yield of 19.42%. Then, SPUP was characterized using chemical analysis, gas chromatography, size-exclusion HPLC chromatography, UV-vis spectra and FT-IR spectrum. The content of total sugar, uronic acid, protein and sulfate radical were 80.48%, 3.21%, 7.12% and 29.14%, respectively. SPUP was a heteropolysaccharide composed of fucose, glucose and galactose in a molar percentage of 27.15:19.34:53.51 with molecular weight of 97.9 kDa. Finally, the strongly against breast cancer activity of SPUP was confirmed by DMBA-induced breast cancer rats model. AS results, SPUP can significantly restrain breast abnormal enlargement, prolong tumor latency and reduced tumor incidence. Immunomodulatory activity and regulating abnormal sex hormones level might contribute to its anticancer activities.
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Affiliation(s)
- Yun Han
- School of Integrated Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shangdong, PR China.
| | - Jun Wu
- School of Chinese Medicine, Shandong College of Traditional Chinese Medicine, Yantai 264199, Shangdong, PR China
| | - Tingting Liu
- Affiliated Huaian Hospital of Xuzhou Medical College, Huaian 223002, Jiangsu, PR China
| | - Youdong Hu
- Affiliated Huaian Hospital of Xuzhou Medical College, Huaian 223002, Jiangsu, PR China
| | - Qiusheng Zheng
- School of Integrated Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shangdong, PR China
| | - Binsheng Wang
- School of Integrated Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shangdong, PR China
| | - Haiyan Lin
- School of Integrated Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shangdong, PR China
| | - Xia Li
- Affiliated Huaian Hospital of Xuzhou Medical College, Huaian 223002, Jiangsu, PR China.
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Sivakumar D, Surapaneni KM, Prabu PC, Hari N, Thiruvasagam P, Rajasekaran M, Sivaraman T. Evaluation of the anticancer properties of the predicted hBaxBH3-mimetic compound 2-hydroxy-3,5-dinitrobenzamide in a mammary carcinogenesis-induced rat model. RSC Adv 2016. [DOI: 10.1039/c5ra23005e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Designing small molecular prototypes having potential to disrupt binding interfaces of pro-apoptotic–anti-apoptotic/BH3-only proteins is a promising strategy in cancer chemotherapy.
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Affiliation(s)
- Dakshinamurthy Sivakumar
- Structural Biology Lab
- Department of Bioinformatics
- School of Chemical and Biotechnology
- SASTRA University
- Thanjavur-613 401
| | | | | | - Natarajan Hari
- Department of Chemistry
- School of Chemical and Biotechnology
- SASTRA University
- Thanjavur-613 401
- India
| | - Ponnusamy Thiruvasagam
- Department of Chemistry
- School of Chemical and Biotechnology
- SASTRA University
- Thanjavur-613 401
- India
| | - Muthu Rajasekaran
- Department of Biotechnology
- School of Chemical and Biotechnology
- SASTRA University
- Thanjavur-613 401
- India
| | - Thirunavukkarasu Sivaraman
- Structural Biology Lab
- Department of Bioinformatics
- School of Chemical and Biotechnology
- SASTRA University
- Thanjavur-613 401
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Cojocneanu Petric R, Braicu C, Raduly L, Zanoaga O, Dragos N, Monroig P, Dumitrascu D, Berindan-Neagoe I. Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. Onco Targets Ther 2015; 8:2053-2066. [PMID: 26273208 PMCID: PMC4532173 DOI: 10.2147/ott.s83597] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Over the years, nutrition and environmental factors have been demonstrated to influence human health, specifically cancer. Owing to the fact that cancer is a leading cause of death worldwide, efforts are being made to elucidate molecular mechanisms that trigger or delay carcinogenesis. Phytochemicals, in particular, have been shown to modulate oncogenic processes through their antioxidant and anti-inflammatory activities and their ability to mimic the chemical structure and activity of hormones. These compounds can act not only by influencing oncogenic proteins, but also by modulating noncoding RNAs such as microRNAs and long noncoding RNAs. Although we are only beginning to understand the complete effects of many natural compounds, such as phytochemicals, researchers are motivated to combine these agents with traditional, chemo-based, or hormone-based therapies to fight against cancer. Since ongoing studies continue to prove effective, herein we exalt the importance of improving dietary choices as a chemo-preventive strategy.
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Affiliation(s)
- Roxana Cojocneanu Petric
- Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Lajos Raduly
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Physiopathology, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, Cluj-Napoca, Romania
| | - Oana Zanoaga
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Nicolae Dragos
- Department of Biology, Babes-Bolyai University, Cluj-Napoca, Romania
- Department of Taxonomy and Ecology, Institute of Biological Research, Cluj-Napoca, Romania
| | - Paloma Monroig
- Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA
| | - Dan Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA
- Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Romania
- Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Propionibacterium acnes Augments Antitumor, Anti-Angiogenesis and Immunomodulatory Effects of Melatonin on Breast Cancer Implanted in Mice. PLoS One 2015; 10:e0124384. [PMID: 25919398 PMCID: PMC4412818 DOI: 10.1371/journal.pone.0124384] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 03/01/2015] [Indexed: 01/11/2023] Open
Abstract
Breast cancer is one of the most invasive cancers with high mortality. The immune stimulating Propionibacterium acnes is a Gram positive bacterium that has the ability to cause inflammation and activate Th1-type cytokine immune response. Antitumor response was associated with the inflammation induced by P. acnes, but the antitumor effect of this bacterium was not evaluated in combination with other agents. The aim of this study was to test the antitumor potential of a combination of melatonin and P. acnes against breast cancer implanted in mice. Balb/C mice were transplanted with EMT6/P cell line and in vivo antitumor effect was assessed for P. acnes, melatonin, and a combination of melatonin and P. acnes. Tumor and organs sections were examined using hematoxylin/eosin staining protocol, and TUNEL colorimetric assay was used to detect apoptosis. The expression of vascular endothelial growth factor (VEGF) was measured in tumor sections and serum levels of INF-γ, and IL-4 were measured to evaluate the immune system function. To evaluate the toxicity of our combination, AST and ALT levels were measured in the serum of treated mice. The combination of melatonin and P. acnes has high efficiency in targeting breast cancer in mice. Forty percent of treated mice were completely cured using this combination and the combination inhibited metastasis of cancer cells to other organs. The combination therapy reduced angiogenesis, exhibited no toxicity, induced apoptosis, and stimulates strong Th1-type cytokine antitumor immune response. The combination of melatonin and P. acnes represents a promising option to treat breast cancer. However, carful preclinical and clinical evaluation is needed before considering this combination for human therapy.
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Maayah ZH, Ghebeh H, Alhaider AA, El-Kadi AO, Soshilov AA, Denison MS, Ansari MA, Korashy HM. Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway. Toxicol Appl Pharmacol 2015; 284:217-26. [DOI: 10.1016/j.taap.2015.02.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Revised: 02/05/2015] [Accepted: 02/06/2015] [Indexed: 10/24/2022]
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Ono M, Takeshima M, Nakano S. Mechanism of the Anticancer Effect of Lycopene (Tetraterpenoids). MECHANISM OF THE ANTICANCER EFFECT OF PHYTOCHEMICALS 2015; 37:139-66. [DOI: 10.1016/bs.enz.2015.06.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Bilal I, Chowdhury A, Davidson J, Whitehead S. Phytoestrogens and prevention of breast cancer: The contentious debate. World J Clin Oncol 2014; 5:705-712. [PMID: 25302172 PMCID: PMC4129534 DOI: 10.5306/wjco.v5.i4.705] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 01/26/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors (ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growth-promoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors (p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high (> 10) µmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability to inhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of “free” unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.
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45
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Bishayee A, Mandal A. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats. Mutat Res 2014; 768:107-118. [PMID: 24451939 DOI: 10.1016/j.mrfmmm.2014.01.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 12/21/2013] [Accepted: 01/02/2014] [Indexed: 06/03/2023]
Abstract
Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight and reversed intratumor histopathological alterations. TPE dose-dependently suppressed proliferating cell nuclear antigen and cyclin D1 expression, induced apoptosis, upregulated proapoptotic protein Bax, downregulated antiapoptotic protein Bcl-2 and diminished the expression of nuclear and cytosolic β-catenin in mammary tumors. Our results clearly provide the first experimental evidence that TPE exerts chemopreventive effect in the classical DMBA model of breast cancer by suppressing abnormal cell proliferation and inducing apoptosis mediated through alteration of Bax/Bcl-2 ratio. Mechanistically, TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during an early-stage breast cancer. These results may encourage further studies to explore full potential of T. portulacastrum phytoconstituents as breast cancer chemopreventive agents.
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Affiliation(s)
- Anupam Bishayee
- Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755, USA.
| | - Animesh Mandal
- Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA
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Ryo K, Takahashi A, Tamaki Y, Ohnishi-Kameyama M, Inoue H, Saito I. Therapeutic effects of isoflavones on impaired salivary secretion. J Clin Biochem Nutr 2014; 55:168-73. [PMID: 25411521 PMCID: PMC4227830 DOI: 10.3164/jcbn.14-49] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 04/30/2014] [Indexed: 01/15/2023] Open
Abstract
Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.
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Affiliation(s)
- Koufuchi Ryo
- Department of Pathology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
| | - Ayako Takahashi
- Department of Pathology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
| | - Yoh Tamaki
- Department of Health and Welfare Services National Institute of Public Health, 2-3-6 Minami, Wako-shi, Saitama 351-0197, Japan
| | - Mayumi Ohnishi-Kameyama
- National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan
| | - Hiroko Inoue
- Department of Pathology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan ; Department of Pharmacotherapy, Nihon Pharmaceutical University, 1028 Komuro, Kitaadachigun Inamachi, Saitama 362-0806, Japan
| | - Ichiro Saito
- Department of Pathology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
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Sahin K, Orhan C, Tuzcu M, Sahin N, Ali S, Bahcecioglu IH, Guler O, Ozercan I, Ilhan N, Kucuk O. Orally Administered Lycopene Attenuates Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats by Modulating Nrf-2/HO-1 and Akt/mTOR Pathways. Nutr Cancer 2014; 66:590-8. [DOI: 10.1080/01635581.2014.894092] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Targets for the Action of Phytoestrogens in Breast Cancer—Focus on Isoflavones and Resveratrol. CURRENT BREAST CANCER REPORTS 2014. [DOI: 10.1007/s12609-014-0141-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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49
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Shen C, Wang S, Shan Y, Liu Z, Fan F, Tao L, Liu Y, Zhou L, Pei C, Wu H, Tian C, Ruan J, Chen W, Wang A, Zheng S, Lu Y. Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice. Food Funct 2014; 5:1422-31. [DOI: 10.1039/c4fo00035h] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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50
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Trejo-Solís C, Pedraza-Chaverrí J, Torres-Ramos M, Jiménez-Farfán D, Cruz Salgado A, Serrano-García N, Osorio-Rico L, Sotelo J. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2013; 2013:705121. [PMID: 23970935 PMCID: PMC3736525 DOI: 10.1155/2013/705121] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Revised: 06/05/2013] [Accepted: 06/19/2013] [Indexed: 12/15/2022]
Abstract
Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.
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Affiliation(s)
- Cristina Trejo-Solís
- Departamentos de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
| | - Jose Pedraza-Chaverrí
- Neurobiología Molecular y Celular INNN-UNAM, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
- Facultad de Química, Universidad Nacional Autónoma de México (UNAM), C.P. 04510, Mexico City, DF, Mexico
| | - Mónica Torres-Ramos
- Unidad Periferica de NeuroCiencias INNN-UNAM, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
| | - Dolores Jiménez-Farfán
- Facultad de Odontología, Universidad Nacional Autónoma de México (UNAM), C.P. 04510, Mexico City, DF, Mexico
| | - Arturo Cruz Salgado
- Facultad de Odontología, Universidad Nacional Autónoma de México (UNAM), C.P. 04510, Mexico City, DF, Mexico
| | - Norma Serrano-García
- Neurobiología Molecular y Celular INNN-UNAM, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
- Facultad de Química, Universidad Nacional Autónoma de México (UNAM), C.P. 04510, Mexico City, DF, Mexico
| | - Laura Osorio-Rico
- Neuroquimica, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
| | - Julio Sotelo
- Departamentos de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía (INNN), C.P. 14269, Mexico City, DF, Mexico
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