title: 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.
authors.affiliation: Molecular Medicine Section, Institute of Neurobiology and Molecular Medicine, National Council of Research, Rome, Italy. mariapia.fuggetta@ims.rm.cnr.it
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Fuggetta
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Atri
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanzilli
authors.forename: Maria
authors.initials: M
authors.lastname: Tricarico
authors.forename: Elda
authors.initials: E
authors.lastname: Cannavò
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Roberto
authors.initials: R
authors.lastname: Falchetti
authors.forename: Giampiero
authors.initials: G
authors.lastname: Ravagnan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; D003606:Dacarbazine; D011065:Poly(ADP-ribose) Polymerases; D000077185:Resveratrol; D000077204:Temozolomide