Synergistic Effects of Lauryl Gallate and Tamoxifen on Human Breast Cancer Cell
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Abstract
Background: Tamoxifen (TAM) is widely used for adjuvant therapy in breast cancer patients. Tamoxifen therapy may lead to serious side effects. Anti-apoptotic substances in combination with chemotherapy drugs can result in additive or synergistic effects. Lauryl gallate (LG), a Gallic acid derivative, has been proven to inhibit tumor growth, without affecting normal cells. This study aimed to investigate the synergistic effect of TAM and LG in breast cancer cell line (MCF-7).
Methods: In this experimental study, performed in ShahreKord University of Medical Science, Iran in 2017, the MCF-7 cells were treated by final concentrations of 10 μM TAM alone, and in combination with 200 μM of LG. We also used EX-527, as SIRT-1 inhibitor to examine the role of SIRT1 in cell apoptosis. BCL-2 and SIRT1 gene expression were measured by real-time PCR method, and cell apoptosis was investigated by flow cytometry.
Results: Tamoxifen alone and in combination with LG decreased BCL-2 expression 2.64±0.75 and 6.38±1.9 fold, respectively, after 48 h (P<0.05). SIRT1 expression was increased 1.67±0.22 and 2.47±0.34 - fold by TAM alone and in combination with LG, respectively (P<0.05). TAM alone and in combination with LG increased the percentage of apoptotic cells 15.79±2.81 and 60.67±6.23 percent, respectively after 48 h (P<0.001).
Conclusion: The combination of LG and TAM is more effective for induction of apoptosis of breast cancer cells, compared to individual use of each. Thus, our data pave the way for new therapeutic options for suppressing breast cancer growth.
References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA: a cancer journal for clinicians. 2009;59(4):225-49.
Furr B, Jordan V. The pharmacology and clinical uses of tamoxifen. Pharmacology & therapeutics. 1984;25(2):127-205.
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. JNCI: Journal of the National Cancer Institute. 1998;90(18):1371-88.
Alagozlu H, Cindoruk M, Unal S. Tamoxifen-induced severe hypertriglyceridaemia and acute pancreatitis. Clinical drug investigation. 2006;26(5):297-302.
Gao FF, Lv JW, Wang Y, Fan R, Li Q, Zhang Z, et al. Tamoxifen induces hepatotoxicity and changes to hepatocyte morphology at the early stage of endocrinotherapy in mice. Biomedical reports. 2016;4(1):102-6.
Aruoma OI, Murcia A, Butler J, Halliwell B. Evaluation of the antioxidant and prooxidant actions of gallic acid and its derivatives. Journal of Agricultural and Food Chemistry. 1993;41(11):1880-5.
Jagan S, Ramakrishnan G, Anandakumar P, Kamaraj S, Devaki T. Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma. Molecular and cellular biochemistry. 2008;319(1-2):51.
Cheng CH, Cheng YP, Chang IL, Chen HY, Wu CC, Hsieh CP. Dodecyl gallate induces apoptosis by upregulating the caspase-dependent apoptotic pathway and inhibiting the expression of anti-apoptotic Bcl-2 family proteins in human osteosarcoma cells. Molecular medicine reports. 2016;13(2):1495-500.
de Cordova CA, Locatelli C, Assunção LS, Mattei B, Mascarello A, Winter E, et al. Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma cell line. Toxicology in Vitro. 2011;25(8):2025-34.
Motawi TK, Abdelazim SA, Darwish HA, Elbaz EM, Shouman SA. Modulation of tamoxifen cytotoxicity by caffeic acid phenethyl ester in MCF-7 breast cancer cells. Oxidative medicine and cellular longevity. 2016;2016.
Sartippour MR, Pietras R, Marquez-Garban DC, Chen H-W, Heber D, Henning SM, et al. The combination of green tea and tamoxifen is effective against breast cancer. Carcinogenesis. 2006;27(12):2424-33.
Ganji-Harsini S, Khazaei M, Rashidi Z, Ghanbari A. Thymoquinone could increase the efficacy of tamoxifen induced apoptosis in human breast cancer cells: An in vitro study. Cell Journal (Yakhteh). 2016;18(2):245.
Malongane F, McGaw LJ, Mudau FN.The synergistic potential of various teas, herbs and therapeutic drugs in health improvement: a review. Journal of the science of food and agriculture. 2017 Nov; 97(14):4679-4689.
Jiang M, Huang O, Zhang X, Xie Z, Shen A, Liu H, et al. Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013;18(1):701-20.
Dhima IT, Peschos D, Simos YV, Gkiouli MI, Palatianou ME1, Ragos VN, et al. Modulation of cisplatin cytotoxic activity against leiomyosarcoma cells by epigallocatechin-3-gallate. Natural Product Research . 2018;32(11):1337-1342
Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, et al. SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. Journal of Biological Chemistry. 2009;284(27):18210-7.
Santolla MF, Avino S, Pellegrino M, De Francesco E, De Marco P, Lappano R, et al. SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer. Cell death & disease. 2015;6(7):e1834.
Kuo S-J, Lin H-Y, Chien S-Y, Chen D-R. SIRT1 suppresses breast cancer growth through downregulation of the Bcl-2 protein. Oncology reports. 2013;30(1):125-30.
| Files | ||
| Issue | Vol 49 No 7 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v49i7.3586 | |
| PMCID | PMC7548506 | |
| PMID | 33083299 | |
| Keywords | ||
| Breast Cancer Lauryl gallate Gene expression Apoptosis Tamoxifen | ||
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