Resveratrol inhibits rhabdomyosarcoma cell proliferation

Abstract

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.

A Resveratrol Analogue Promotes ERKMAPK–Dependent Stat3 Serine and Tyrosine Phosphorylation Alterations and Antitumor Effects In Vitro against Human Tumor Cells

“…In the present study, however, it is notable that this analog is more potent than resveratrol in suppressing the viability and growth of the human glioma, breast, and pancreatic cancer cells, with a preferential effect against U251MG glioma cells, while only weakly affecting normal NIH3T3 at the highest dose tested. The cell growth inhibition, cell cycle block at the G2/M phase, and apoptosis induced by Cmpd1 in U251MG cells all parallel the reported inhibitory effects of resveratrol in human breast, pancreatic, prostate, rhabdomyosarcoma, and other tumor cells (Hadi et al, 2000;Chow et al, 2005;Kotha et al, 2006;Meeran and Katiyar, 2008;Quoc Trung et al, 2013). Cmpd1-induced biologic responses are preceded by decreases in the expression of cell cycle regulatory and apoptotic genes.…”

Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells

“…In addition, it prevents chemical carcinogen-induced epithelial cell transformation (Roy et al, 2009;Sengottuvelan et al, 2009) and inhibits neoangiogenesis (Tseng et al, 2004;Dann et al, 2009). Several studies have shown that RES inhibited the growth of different human cancer cell lines, including human oral squamous carcinoma, promyelocytic leukemia, breast, lung, prostate, rhabdomyosarcoma, and colon cancer cells (Elattar and Virji, 1999;Joe et al, 2002;Pozo-Guisado et al, 2002;Opipari et al, 2004;Chow et al, 2005;Stervbo et al, 2006;Alkhalaf, 2007;Lee et al, 2008;Benitez et al, 2009;Kim et al, 2009;Malhotra et al, 2011). This effect has been associated with the ability of RES to arrest cell cycle progression (Wolter et al, 2001;Bai et al, 2010), to promote cell differentiation (Wolter and Stein, 2002), and to induce programmed cell death (Park et al, 2001;Brito et al, 2008;Lin et al, 2008).…”

Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

“…In human RMS RD cells (FN-RMS), resveratrol exerts radioprotective effects at the concentration of 15 μM while it shows cytotoxic effects at 60 μM [ 158 ]. The combination of different concentrations of resveratrol (15, 30, and 60 μM) with doses of 50 Gy and 100 Gy of IR at different times post-IR (0 h, 24 h, 48 h), clearly shows that 15 μM resveratrol combined with 50 Gy of IR is capable to reduce the DNA damage after 48 h in RD cells and that the combination with 100 Gy renders the cells more resistant to DNA damage either after 24 h and 48 h. Interestingly, although Chow et al demonstrated that doses of resveratrol between 50 μM and 100 μM reduced the cell proliferation of RD cells [ 159 ], the combination of 60 μM of resveratrol with high doses of IR does not show statistically significant cytotoxic effects [ 158 ]. Although resveratrol acts in a dose-dependent manner, further studies are needed to really understand whether the effect of RT on human RMS can be enhanced by the treatment with high concentrations of resveratrol or not.…”