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The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells
Author(s) -
Alayev Anya,
Berger Sara Malka,
Kramer Melissa Y.,
Schwartz Naomi S.,
Holz Marina K.
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24997
Subject(s) - mtorc1 , autophagy , pi3k/akt/mtor pathway , downregulation and upregulation , cancer research , resveratrol , protein kinase b , apoptosis , estrogen receptor , cancer , cancer cell , signal transduction , breast cancer , pharmacology , chemistry , microbiology and biotechnology , biology , medicine , biochemistry , gene
Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) is a frequent event in breast cancer and current efforts are aimed at targeting the mTORC1 signaling pathway in combination with other targeted therapies. However, patients often develop drug resistance in part due to activation of the oncogenic Akt signaling and upregulation of autophagy, which protects cancer cells from apoptosis. In the present study we investigated the effects of combination therapy of rapamycin (an allosteric mTORC1 inhibitor) together with resveratrol (a phytoestrogen that inhibits autophagy). Our results show that combination of these drugs maintains inhibition of mTORC1 signaling, while preventing upregulation of Akt activation and autophagy, causing apoptosis. Additionally, this combination was effective in estrogen receptor positive and negative breast cancer cells, underscoring its versatility. J. Cell. Biochem. 116: 450–457, 2015. © 2014 Wiley Periodicals, Inc.