Effect of trans-resveratrol on signal transduction pathways involved in paclitaxel-induced apoptosis in human neuroblastoma SH-SY5Y cells

• Published in: Neurochemistry international 2003-04, Vol.42 (5), p.419-429
• Main Authors: Nicolini, G., Rigolio, R., Scuteri, A., Miloso, M., Saccomanno, D., Cavaletti, G., Tredici, G.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Caspase 7; Caspases - biosynthesis; Caspases - genetics; Cell Death - drug effects; Cell Line; DNA - biosynthesis; DNA - genetics; Fundamental and applied biological sciences. Psychology; Humans; Immunoblotting; Mitogen-Activated Protein Kinases - biosynthesis; Mitogen-Activated Protein Kinases - genetics; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Paclitaxel - pharmacology; Paclitaxel-induced apoptosis; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-raf - biosynthesis; Proto-Oncogene Proteins c-raf - genetics; Resveratrol; Signal Transduction - drug effects; Stilbenes - pharmacology; trans-Resveratrol; Transduction; Tumor Cells, Cultured
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(02)00132-8

trans-Resveratrol (3,4′,5-trihydroxystilbene) is able to significantly reduce paclitaxel-induced apoptosis in the human neuroblastoma (HN) SH-SY5Y cell line, acting on several cellular signaling pathways that are involved in paclitaxel-induced apoptosis. trans-Resveratrol reverses phosphorylation of Bcl-2 induced by paclitaxel and concomitantly blocks Raf-1 phosphorylation, also observed after paclitaxel exposure, thus suggesting that Bcl-2 inactivation may be dependent on the activation of the Raf/Ras cascade. trans-Resveratrol also reverses the sustained phosphorylation of JNK/SAPK, which specifically occurs after paclitaxel exposure. Overall, our observations demonstrate that (a) the toxic action of paclitaxel on neuronal-like cells is not only related to the effect of the drug on tubulin, but also to its capacity to activate several intracellular pathways leading to inactivation of Bcl-2, thus causing cells to die by apoptosis, (b) trans-resveratrol significantly reduces paclitaxel-induced apoptosis by modulating the cellular signaling pathways which commit the cell to apoptosis.