Dual Effects of Resveratrol on Cell Death and Proliferation of Colon Cancer Cells

Abstract

Colorectal cancer remains a main cause of deaths worldwide, and novel agents are being searched to treat this disease. Polyphenols have emerged as promising therapeutic tools in cancer. Resveratrol (3,5,4'-trihydoxy-trans-stilbene) induces cell death in different tumor cell lines, and it also stimulates the proliferation of specific breast and prostate cancer cell lines. Here, we studied the impact of resveratrol over a 100-fold concentration range on cell death and proliferation of HT-29 colorectal adenocarcinoma cells. After 96 h of treatment, a biphasic pattern was observed. At lower concentrations (1 and 10 μmol/l), resveratrol increased the cell number, as did the polyphenol quercetin. At 50 or 100 μmol/l, resveratrol reduced the cell number and increased the percentage of apoptotic or necrotic cells, thus indicating cytotoxicity. On HCT116 colon cancer cells, however, no proliferative properties of resveratrol were observed. Resveratrol-induced cytotoxicity on HT-29 cells was associated with NADPH oxidase activation and increased levels of histone γH2AX, a marker of DNA damage, paralleled by enhanced sirtuin 6 levels, likely as a repair mechanism. Overall, resveratrol may be an effective tool in anti-tumor chemotherapy. However, since under some conditions it may favor tumor cell growth, appropriate local concentrations must be achieved to minimize unwanted effects of resveratrol.

A novel synthetic flavonoid with potent antibacterial properties: In vitro activity and proposed mode of action

“…Overall, the tested compound exerted a biphasic effect on normal Vero cells in terms of proliferation and cytotoxicity. Similar effects of polyphenolic compounds were also signaled on other cell lines, the biphasic behavior being dose-dependent [ 32 ].…”

SIRT1–NOX4 signaling axis regulates cancer cachexia

“…It is worth mentioning, however, that although SIRT1 stabilization provided similar survival benefit as targeting NOX4 (Fig. S5 D), some studies have suggested that SIRT1 modulation may have potential therapeutic limitations, due in part to a prooxidant role or tumor growth-inducing properties (de la Lastra and Villegas, 2007;San Hipólito-Luengo et al, 2017). Depending on the cellular context, SIRT1 can act either as a tumor suppressor or as a tumor promoter and may have different signaling targets in different cell types (Chen et al, 2005;Yeung et al, 2004).…”

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

“…At concentrations, 1-10 µM RES increased about 2-fold a number of cells whereas at 50 µM and 100 µM, the percentage of necrotic and apoptotic cells was reduced by 76% and 90%, respectively. RES-induced cytotoxicity was associated with NADP oxidase activation and increased level of histone GH2AX, a marker of DNA damage [50].…”