Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis.
In previous studies we demonstrated that resveratrol acts in an antiapoptotic manner on the paclitaxel-treated human neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic pathways induced by the antineoplastic drug. In the present study we evaluated the antiapoptotic effect of resveratrol, studying its activity on cell cycle progression. We determined the mitotic index of cultures exposed to resveratrol and paclitaxel alone or in combination, the cell cycle distribution by flow cytometric analysis (FACS), and the modulation of some relevant cell cycle regulatory proteins. Resveratrol is able to induce S-phase cell arrest and this interference with the cell cycle is associated with an increase of cyclin E and cyclin A, a downregulation of cyclin D1, and no alteration in cyclin B1 and cdk 1 activation. The resveratrol-induced S-phase block prevents SH-SY5Y from entering into mitosis, the phase of the cell cycle in which paclitaxel exerts its activity, explaining the antiapoptotic effect of resveratrol.
Rigolio
R
R
Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy.
Miloso
M
M
Nicolini
G
G
Villa
D
D
Scuteri
A
A
Simone
M
M
Tredici
G
G
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D013267:Stilbenes; D016200:Maturation-Promoting Factor; D017239:Paclitaxel; D000077185:Resveratrol