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Atorvastatin Enhances Anti-Apoptotic Effects of Tamoxifen on Melanoma Cancer Cells Publisher Pubmed



Ghasemi M1 ; Malek M1 ; Haghjooy JS1 ; Ghasemi A1 ; Naji EH1 ; Vaseghi G2
Authors
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Authors Affiliations
  1. 1. Applied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Bratislava Medical Journal Published:2019


Abstract

AIM: Tamoxifen engages mitochondrial estrogen receptor beta as an antagonist, increases mitochondrial cytotoxicity and induces tumor cell death. Tamoxifen also engages plasma membrane estrogen receptor alpha as an agonist, while it is suggested that in some users its activation is put into action by mechanism of resistance to tamoxifen. Apoptotic inducers have been shown to promote tamoxifen-induced cell death, which might be of great importance in overcoming tamoxifen resistance. Considering the pleiotropic effects of statins, in the present study, we investigated the effects of atorvastatin on tamoxifen-induced intrinsic apoptotic pathway activity in melanoma cells. METHODS: Melanoma B16F10 cells were treated for 24 and 48 h with various concentrations of tamoxifen, atorvastatin and combination of tamoxifen + atorvastatin. Cells with no treatment were considered a control group, and the study was then followed by quantitative RT-PCR assay. Bax and cytochrome c gene expressions were calculated by ΔΔct method. RESULTS: Co-treatment of atorvastatin + tamoxifen could strongly enhance the expression of pro/apoptotic factors of Bax and cytochrome c in melanoma cells compared to the tamoxifen and atorvastatin groups. CONCLUSION: In general, we conclude that the atorvastatin-induced increase in Bax and cytochrome c gene expression might be a permissive response to tamoxifen-induced cell deat. © Comenius University.
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