Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling pathway.
Resveratrol has been reported to possess therapeutic effects for various cancers including colon cancers. In this article, the molecular basis of resveratrol with emphasis on its ability to control intracellular signaling cascades of adenosine monophosphate (AMP)-activated protein kinase (AMPK) responsible for inducing apoptosis in drug-resistant cancer cells was investigated. Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of cancer control. We have investigated the effects of resveratrol on apoptosis in relation to AMPK in HT-29 cells shown chemoresistant to a cancer chemotherapeutic drug, etoposide. Resveratrol exhibited a variety of molecular events in etoposide-based combination therapy in HT-29 colon cancer cells including the AMPK activation, inhibition of cell growth, induction of apoptosis, and reactive oxygen species (ROS) generation. The involvement of AMPK signaling cascade in resveratrol-based cancer therapy was clearly shown by comparing the conditions of AMPK activated states and inactivated states. We have identified ROS as an upstream regulator of AMPK. Further investigation warrants to elucidate the mechanism by which resveratrol generates ROS and AMPK activation.
Hwang
Jin-Taek
JT
Department of Food and Nutrition, Hannam University, 133 Ojeong-dong Daedeok-gu, Daejeon 306-791, Korea.
Kwak
Dong Wook
DW
Lin
Sun Kyo
SK
Kim
Hye Min
HM
Kim
Young Min
YM
Park
Ock Jin
OJ
D055372:AMP-Activated Protein Kinases; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D009097:Multienzyme Complexes; D013267:Stilbenes; D005047:Etoposide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol