Potential of resveratrol in anticancer therapy

T Demirtas1, G Gacar2, T Utkan1, N Gacar1, B Akpinar2, E Karaoz2, Z Utkan0. 1Kocaeli University Medical School, Pharmacology 41380, Turkey, 2Kocaeli University, Stem Cell and Gene Therapies 41380, Turkey, 3Kocaeli University Medical School, General Surgery 41380, Turkey

Breast cancer is one of the major causes of death among women. Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by interventing at one or more stages of carcinogenesis. Resveratrol, a natural product found in the diet of humans also in the plant in response to an invading fungus, stress, injury, infection, or ultraviolet irradiation has been shown to function as a cancer chemopreventive agents. Its synthesis from p-coumaroyl CoA and malonyl CoA is induced by stress, injury, infection or UV-irradiation. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases.

Due to the anticarcinogenic effect of resveratrol is quite a broad spectrum of employees in this area has been the focus of attention. Resveratrol regulates multiple cellular and molecular events associated with tumor development. In vivo, resveratrol inhibits three major steps of carcinogenesis: initiation, promotion, and progression. Caspase activation and apoptosis, inhibition of activator protein -1 (AP-1), inhibition of mitogen-proliferation are the some of the mechanisms which are shown. In another study, it was shown that resveratrol and derivatives suppress the DNA damage caused by HL-60 cell proliferation by a powerful way and made it byforcing the HL-60 cells to apoptosis. In the present study, we aimed to investigate the in vitro effects of resveratrol on breast cancer cell line MCF7 cancer cells with various techniques. For this purpose, MCF7 (1x105) were inoculated in 6-well plates. All cell lines were maintained in Dulbecco\'s modified Eagle\'s medium, supplemented with 10% fetal bovine serum, 2 mM glutamine, 100 U/l penicillin and 100 U/l streptomycin and were cultured at 37°C in a humid atmosphere consisting of 5% CO2 and 95% air. After 2 hours later, resveratrol was used at various concentrations (0, 1, 10, 20, 40µM) for 4 days. Significant differences were determined using one way ANOVA followed by Tukey’s post hoc test. We determined the proliferation capacity and viability using WST, and 72 hours later apoptosis level using AnnexinV-PI staining by using flow cytometer (Each experiment was repeated 3 times).

As a result, we found a sharp decline in proliferation 40µM concentration (1.27±0.01) compared to control group (2.15±0.01) (p<0.001). Application of resveratrol resulted in a dose-dependent decrease in WST-1 proliferation assay (1, 10, 20µM) (1.82±0.01; 1.62±0.01; 1.55±0.01). We obtained sphere using the same cell lines. In order to determine the effect of different doses of resveratrol on this sphere ATP tumorchemosensitivity test was performed. We obtained similar results with AnnexinV-PI staining according to the percentage of apoptotic cells (dose 1, 10, 20, 40 µM) (21.08±0.05; 36.68±0.09; 82.64±0.13; 91.84±0.08) compared to control (16.72±0.11) (p<0.001).

In conclusion, we are in the belief that resveratrol providing a major direct support to stem cell therapy, as an alternative treatment option in the treatment of many diseases, is a big step to be taken noted promising results.

Aggarwal, B.B. et al ., Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004. 24: 2783–2840.