Premium
Combination of Rapamycin and Resveratrol for Treatment of Bladder Cancer
Author(s) -
Alayev Anya,
Salamon Rachel S.,
Schwartz Naomi S.,
Berman Adi Y.,
Wiener Sara L.,
Holz Marina K.
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25443
Subject(s) - pi3k/akt/mtor pathway , resveratrol , tsc1 , cancer research , protein kinase b , rptor , bladder cancer , autophagy , cancer cell , cancer , programmed cell death , mtorc1 , pharmacology , chemistry , medicine , signal transduction , biology , apoptosis , microbiology and biotechnology , biochemistry
Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin‐induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1 −/− MEF cells, and not in wild‐type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436–446, 2017. © 2016 Wiley Periodicals, Inc.