Spontaneous and 5-fluorouracil-induced centrosome amplification lowers the threshold to resveratrol-evoked apoptosis in colon cancer cells

Abstract

We recently reported that caspase-6 activation is a major molecular event underlying resveratrol-triggered apoptosis in HCT116 colon cancer cells with or without p53. In the present study, we investigated the relationship between centrosome amplification and apoptosis sensitivity in cancer cells. We found that centrosome amplification, which occurs spontaneously in cancer cells, could be induced by a subtoxic concentration of 5-fluorouracil. Cancer cells with centrosome amplification, either spontaneous or 5-fluorouracil-induced, were more sensitive to apoptosis induction by resveratrol. In cancer cells, a subtoxic concentration of 5-fluorouracil also enhanced resveratrol-evoked caspase-6 activation. Functional loss of p53 promoted spontaneous, not 5-fluorouracil-induced, centrosome amplification. We conclude that centrosome amplification, either spontaneous or 5-fluorouracil-induced, confers higher apoptosis sensitivity to cancer cells. Drug induction of centrosome amplification might be a novel chemosensitization approach to cancer therapy. © 2009 Elsevier Ireland Ltd. All rights reserved.