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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.
Abbreviations
| ANOVA | = | Analysis of variance |
| ECL | = | Enhanced chemiluminescence |
| EDTA | = | Ethylenediaminetetraacetic acid |
| EGTA | = | Ethylene glycol tetraacetic acid |
| FBS | = | Fetal bovine serum |
| FITC | = | Fluorescein isothiocyanate |
| IC50 | = | Half-maximal inhibitory concentration |
| LDH | = | Lactate dehydrogenase |
| MTT | = | 3-(4, 5-dimethylthiazol-2-yl)-2, 5diphenyltetrazolium bromide |
| NAD | = | Nicotinamide adenine dinucleotide |
| NADPH | = | Nicotinamide adenine dinucleotide phosphate |
| PBS | = | Phosphate-buffered saline |
| PI | = | Propidium iodide |
| PVDF | = | Polyvinylidene fluoride |
| RLU | = | Relative light units |
| SEM | = | Standard error of the mean |
| X/XO | = | Xanthine/Xanthine oxidase |
Funding
This study was supported by grants from Plan Nacional de I+D (SAF2014-52762-R) and Proyecto de Excelencia de la Junta de Andalucía (P12-AGR-430).
Conflict of Interest
The authors declare that there is no conflict of interest to be disclosed.