Resveratrol inhibits proliferation and promotes apoptosis of neuroblastoma cells: role of sirtuin 1.
Resveratrol prolongs lifespan and prevent cancer formation; however, the mechanisms are not understood. Here we evaluated the cell-cycle inhibition and apoptosis of resveratrol in B65 neuroblastoma cells, and we also studied the effects of resveratrol on the mammalian silent information regulator 2 (SIRT1). Results show that resveratrol reduces cell viability and causes apoptosis at 24 h of treatment. Resveratrol partially blocked cell proliferation, and significantly increased the fraction of cells arrested in the S phase. The role of SIRT1 in cell-cycle effects mediated by resveratrol was studied through changes in the expression of SIRT1 using western blot. Exposure to resveratrol decreased SIRT1 content, concomitant with an increase in the acetylated form of sirtuin substrates p53 and NFκ-β. Treatment of B65 neuroblastoma cells with resveratrol also reduced the content of the phosphorylated form of AKT. Exposure to the SIRT1 inhibitors nicotinamide and sirtinol altered neither cell viability nor the fraction of apoptotic cells. Furthermore, when cells were exposed simultaneously to resveratrol and nicotinamide or sirtinol, no changes were observed in the fraction of apoptotic cells. Our results show that a decrease in SIRT1 content, caused by exposure to resveratrol, does not appear to be involved in cell-cycle arrest or activation of apoptosis.
Pizarro
Javier G
JG
Institut de Biomedicina (IBUB), Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
Verdaguer
Ester
E
Ancrenaz
Virginie
V
Junyent
Felix
F
Sureda
Francesc
F
Pallàs
Mercè
M
Folch
Jaume
J
Camins
Antoni
A
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D001549:Benzamides; D016328:NF-kappa B; D009284:Naphthols; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C439060:sirtinol; D014803:Vitamin B Complex; D009536:Niacinamide; D051057:Proto-Oncogene Proteins c-akt; D056564:Sirtuin 1; D000077185:Resveratrol