Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo.
It was reported recently that resveratrol could sensitise a number of cancer cell lines to the anticancer actions of several other cancer drugs, including paclitaxel. In the present study, we further investigated whether resveratrol could sensitise human breast cancer cells to paclitaxel-induced cell death. Unexpectedly, we found that resveratrol strongly diminished the susceptibility of MDA-MB-435s, MDA-MB-231 and SKBR-3 cells to paclitaxel-induced cell death in culture, although this effect was not observed in MCF-7 cells. Using MDA-MB-435s cells as a representative model, a similar observation was made in athymic nude mice. Mechanistically, the modulating effect of resveratrol was partially attributable to its inhibition of paclitaxel-induced G(2)/M cell cycle arrest, together with an accumulation of cells in the S-phase. In addition, resveratrol could suppress paclitaxel-induced accumulation of reactive oxygen species (ROS) and subsequently the inactivation of anti-apoptotic Bcl-2 family proteins. These observations suggest that the strategy of concomitant use of resveratrol with paclitaxel is detrimental in certain types of human cancers. Given the widespread use of resveratrol among cancer patients, this study calls for more preclinical and clinical testing of the potential benefits and harms of using resveratrol as a dietary adjuvant in cancer patients.
Fukui
Masayuki
M
Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Yamabe
Noriko
N
Zhu
Bao Ting
BT
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D051020:bcl-X Protein / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051020:bcl-X Protein; D017239:Paclitaxel; D000077185:Resveratrol