In vitro antitumour activity of resveratrol in human melanoma cells sensitive or resistant to temozolomide

Abstract

Resveratrol, a polyphenol present in many plant species, exhibits a wide range of biological and pharmacological activities both in vitro and in vivo. It has been shown to exert a potent chemopreventive effect in carcinogenesis models and to induce cell growth inhibition and apoptosis in human tumour cells, including melanoma cells. Malignant melanoma is considered to be a chemotherapy-refractory tumour, and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. To further evaluate the therapeutic potential of resveratrol in the treatment of melanoma, we selected three human melanoma cell lines with different levels of resistance to temozolomide (TMZ), an antitumour triazene compound. The cell lines were subjected to resveratrol treatment and analysed for cell growth inhibition, cell cycle perturbation and apoptosis induction. We found that resveratrol markedly impaired proliferation of both the TMZ-sensitive M14 and the TMZ-resistant SK-Mel-28 and PR-Mel cell lines. The latter cell line was two-fold more resistant to the drug than M14 and SK-Mel-28 cells. The sensitivity of normal human keratinocytes to resveratrol was found to be significantly higher than that of M14 and SK-Mel-28 cells and similar to that of the PR-Mel cell line. This suggests a possible good in vivo therapeutic index for resveratrol. Our results also show that the growth-inhibitory effect of resveratrol on melanoma cells is mainly due to its ability to induce S-phase arrest and apoptosis. Taken together, our data indicate that resveratrol is an interesting candidate for the treatment of advanced melanoma.

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

“…Both compounds have been found to inhibit numerous cell surface protein kinases and both exhibit cytotoxic effects in a variety of tumor cell lines [Zheng and Ramirez, 1999;Fuggetta et al, 2004;Larrosa et al, 2004;Pozo-Guisado et al, 2005]. These compounds have also been found to inhibit EC tube differentiation in vitro [Belleri et al, 2005], thus indirectly supporting the relevance of cell surface F 1 F O ATP synthase to angiogenesis and tumor biology.…”

Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer

“…This could be the case of the combination with 5-fluorouracil (5-Fu) which is a classic drug used in colorectal and hepatoma chemotherapy. Indeed, it was reported that resveratrol can exert synergic effect with this drug to inhibit hepatocarcinoma cell proliferation by the induction of apoptosis [236,237].…”

Diversity of Pharmacological Properties in Chinese and European Medicinal Plants: Cytotoxicity, Antiviral and Antitrypanosomal Screening of 82 Herbal Drugs

“…Paeonia lactiflora, which belongs to the Paeoniaceae family, is known as one of the richest sources of various resveratrol derivatives [81]. These phytoestrogens are known to exert strong antioxidant activity [81] and to inhibit growth of several cancer cell lines [82,83], including a colon human cell line [84]. Recently, the antiproliferative effects of essential oils obtained from Platycladus orientalis on human renal adenocarcinoma and amelanotic melanoma cells have been reported [85].…”