Possible Interaction: Fluorouracil and Resveratrol

“The combination of 5-FU and Res significantly increased the percentage of apoptotic cells and the level of activated caspase-3, cleaved PARP and p53 proteins as well as increased the Bax/Bcl-2 ratio.”

“The combination of Res and 5-FU demonstrates synergistic efficacy, causing tumor regression in a two-stage model of mouse skin carcinogenesis induced by DMBA and TPA.”

“The presented results provide the first evidence that Res can enhance the anti-tumor potency of 5-FU by inducing S-phase arrest.”

“This effect was confirmed by in vivo findings identifying a vasoprotecting strategy by the adjunct therapy of 5-FU with Resveratrol.”

“Methods: We investigated whether resveratrol modulates the effects of 5-Fluorouracil (5-FU) and TNF-β on the malignant potential of human colorectal cancer (CRC) cells (HCT116) and their corresponding isogenic 5-FU-chemoresistant derived clones (HCT116R) in 3D-alginate tumor microenvironment.”

“Our results demonstrate that resveratrol can potentiate the anti-tumor effects of 5-FU on CRC cells by chemosensitizing them, inhibiting an EMT phenotype via up-regulation of intercellular junctions and by down-regulation of NF-κB pathway.”

“ Resveratrol blocked the proliferation of all four CRC cell lines and synergized the invasion inhibitory effects of 5-FU.”

“Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect.”

“Importantly, the combination treatment with RES and 5-FU induced a remarkably synergistic enhancement of growth inhibition and apoptosis through the additional suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells.”

“Data obtained showed additional effects of RSV to 5-FU treatments on the increase ofapoptotic events, and suggested alternative approaches to obtain a stronger antitumor response, and diminished side-effects when low concentrations of anti-cancer drugs are used.”

“A significant inhibition of cell proliferation, migration, and increased apoptosis were observed when moderate concentration of Res (15 microM) was associated with very low concentration of 5-FU (0.5 microM).”

“Since combined treatment using 5-FU with resveratrol resulted in a significant decrease in long-term cell survival, we investigated the possible basis of this synergistic interaction at a molecular level, focusing on oxidative stress as a possible mediator of cell death.”

“Cancer cells with centrosome amplification, either spontaneous or 5-fluorouracil-induced , were more sensitive to apoptosis induction by resveratrol.”