Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: The roles of caspase-6 and p53

Abstract

We have reported that resveratrol (RSV) evoked apoptosis through caspase-6 activation in HCT116 human colon cancer cells wild-type (p53+/+) or knockout (p53-/-) for p53. In this study, the role of caspase-6 activation in 5-fluorouracil (5-FU)-elicited apoptosis as well as the combination effects between RSV and 5-FU on their apoptosis induction was further investigated in the same colon cancer cell model. The combination effects were determined by calculation of combination indices (CI). We found that 5-FU triggered apoptosis and caspase-6 activation in the cancer cells, which were entirely abrogated by caspase-6 inhibitors. RSV (200 µM) increased 5-FU-triggered apoptosis and caspase-6 activation. Lower doses (25 or 50 µM) inhibited 5-FU-mediated apoptosis and caspase-6 activation only in p53+/+ cells. Moreover, G1-arrest of the p53+/+ cells was elicited by lower doses of RSV and 5-FU in combination, but not with either agent alone. RSV (200 µM) interacted with 5-FU in a synergistic manner (mean CI < 0.9). At lower doses (25 or 50 µM), it interacted with 5-FU in antagonistic (mean CI > 1.1) and additive manners (0.9 < mean CI

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Expression of Concern: Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: The roles of caspase-6 and p53