Two hits are better than one: synergistic anticancer activity of α-helical peptides and doxorubicin/epirubicin
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Jing Zhao1,3, Yibing Huang1,2,3, Dong Liu1,3, Yuxin Chen1,2,3
1Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China
2National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China
3School of Life Sciences, Jilin University, Changchun, China
Yuxin Chen, e-mail: [email protected]
Keywords: Anticancer peptides, doxorubicin/epirubicin, synergy, mechanism of action, xenograft model
Received: September 17, 2014 Accepted: November 15, 2014 Published: December 19, 2014
This study explored combinational anticancer therapy using α-helical peptides HPRP-A1/HPRP-A2 with the chemical drugs doxorubicin (DOX) and epirubicin (EPI). The in vitro activity of these drugs against different cancer cell lines was synergistically increased, as was their activity in a HeLa xenograft model in BALB/c nude mice. We delineated the mechanism of this synergy by studying the apoptosis pathway and morphologic changes in the HeLa cell membrane. The mechanism of the HPRP-A1/DOX combination was found to involve enhanced apoptosis, which seemed to be caspase-dependent and involved both the extrinsic and intrinsic parts of the caspase cascade in HeLa cells. Combined application of HPRP-A1 and DOX at low concentrations was significantly more effective than either drug alone against HeLa tumors in the mouse xenograft model. This type of combination therapy appears to have great clinical potential.
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