AIM:To investigate the inhibitory effects of resveratrol on chondrosarcoma and the relation with mitochondrial and PI3K/Akt pathways. METHODS:Chondrosarcoma SW1353 cells were treated with resveratrol at concentrations of 25, 50 and 100 μmol/L for the time intervals of 24 h, 48 h and 72 h. The viability and apoptosis of the SW1353 cells in the presence or absence of resveratrol were analyzed by CCK8 assay and Hoechst 33258 staining, respectively. The protein levels of Bcl-2, Bax, activated caspase-3, Akt and p-Akt were detected by Western blotting. The cell migration ability was determined by wound scratch assay. RESULTS:Exposure of the cells to resveratrol resulted in a decrease in the cell viability in a dose- and time-dependent manner (P<0.05). visible nuclei with apoptotic characteristics in resveratrol group were observed. The protein levels of activated caspase-3 and Bax were increased, and Bcl-2 and p-Akt were decreased compared with control group. The total Akt were not significantly changed. Resveratrol also significantly reduced the migration of tumor cells. CONCLUSION:Resveratrol induces apoptosis of chondrosarcoma, which plays a role of part through mitochondrial and PI3K/Akt signaling pathways.
de la Lastra CA, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications[J]. Biochem Soc Trans, 2007, 35(Pt 5): 1156-1160.
[2]
Gusman J, Malonne H, Atassi G, et al. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol[J]. Carcinogenesis, 2001, 22(8):1111-1117.
[3]
Cal C, Garban H, Jazirehi A, et al. Resveratrol and cancer: chemoprevention, apoptosis, and chemoimmunosensitizing activities[J]. Curr Med Chem Anti-Cancer Agents, 2003, 3(2):77-93.
[4]
Whitlock NC, Baek SJ. The anticancer effects of resveratrol: modulation of transcription factors[J]. Nutrition Cancer, 2012, 64(4):493-502.
Li Y, Zhu W, Li J, et al. Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1[J]. Oncol Reports, 2013, 30(6):2820-2828.
[9]
Bhardwaj A, Sethi G, Vadhan-Raj S, et al. Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-κB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells[J]. Blood, 2007, 109(6):2293-2302.
[10]
Drrie J, Gerauer H, Wachter Y, et al. Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells[J]. Cancer Res, 2001, 61(12):4731-4739.
[11]
Pozo-Guisado E, Merino JM, Mulero-Navarro S, et al. Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-κB[J]. Int J Cancer, 2005, 115(1):74-84.
[12]
Almhanna K, Strosberg J, Malafa M, et al. Targeting Akt protein kinase in gastric cancer[J]. Anticancer Res, 2011, 31(12):4387-4392.
[13]
Riggio M, Polo ML, Blaustein M, et al. PI3K/Akt pathway regulates phosphorylation of steroid receptors, hormone independence and tumor differentiation in breast cancer[J]. Carcinogenesis, 2012, 33(3):509-518.
[14]
Papadimitrakopoulou V. Development of PI3K/Akt/mTOR pathway inhibitors and their application in personalized therapy for non-small-cell lung cancer[J]. J Thoracic Oncol, 2012, 7(8):1315-1326.
[15]
Villalba JM, Francisco J. Sirtuin activators and inhibitors[J]. Biofactors, 2012, 38(5):349-359.