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) r...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2007-01, Vol.1095 (1), p.441-448
Main Authors: HWANG, JIN-TAEK, KWAK, DONG WOOK, LIN, SUN KYO, KIM, HYE MIN, KIM, YOUNG MIN, PARK, OCK JIN
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases
AMPK
Antineoplastic Agents, Phytogenic - pharmacology
Antineoplastic Combined Chemotherapy Protocols - pharmacology
apoptosis
Apoptosis - drug effects
chemoresistant
Drug Resistance, Neoplasm - drug effects
etoposide
Etoposide - pharmacology
HT-29 cells
HT29 Cells
Humans
Multienzyme Complexes - metabolism
Multienzyme Complexes - physiology
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - physiology
resveratrol
Signal Transduction - drug effects
Stilbenes - pharmacology
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Summary::  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.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1397.047