| Curcumin and its anti-cancer effect have been studied for nearly30years. However,the solubility of curcumin in water is poor, and it has interaction with a wide range ofproteins. All these characters have negative effects on its anti-cancer activity. Previously，we synthesized a series of curcumin analogues which are more soluble in water thancurcumin, and more potential inhibitor of TrxR than curcumin. In this research, we focus onthe anti-cancer activity of B5and its mechanism in vitro. Our research was to enrich thecurcumin analogue family, and provide theory basis for further research on TrxR inhibitorsas well.CaSki and SiHa cells were cultured in DMEM medium. We investigated thecytotoxicity of B5on CaSki and SiHa cells via MTT assay. We examined the cell cycledistribution and apoptosis induced by B5in CaSki and SiHa cells by the flow cytometry. The ROS accumulation in CaSki and SiHa cells induced by B5was detected via DCFH-DAfluorescent probe. We examined MMP (mitochondrial membrane potential) changes andapoptotic pathways in CaSki and SiHa cells via JC-1fluorescent probe and Western Blot,respectively. We also determined the effects of B5on Trx system in CaSki and SiHa cells.Our results indicate that B5is an efficient anti-cancer compound in vitro. The IC50values of B5at48h were5.3μM and6.2μM in CaSki and SiHa, respectively. B5inducedcell cycle arrest (G2/M phase) and apoptosis in both cell lines. B5induced accumulation ofROS in a time dependent manner and accumulation of oxidized Trx in a dose dependentmanner in both cell lines. Furthermore, B5induced reduction of MMP. We also found thedegradation of XIAP and cleavage of PARP, caspase-3, caspase-8and caspase-9with B5treatment.Conclusion: Curcumin analogue B5is an efficient anti-cancer compound in vitro. Theanti-cancer mechanism of B5: B5induced oxidative stress in cancer cells via inhibition ofTrxR which will further disrupt MMP and mitochondria function. Then B5inducedapoptosis via the mitochondria pathway. |
PDF Full Text Request