title: Two hits are better than one: synergistic anticancer activity of α-helical peptides and doxorubicin/epirubicin.
abstract: 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.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.|School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D015251:Epirubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: C576822:Liver enriched gene 1 protein, mouse; D010455:Peptides; D011506:Proteins; D015251:Epirubicin; D004317:Doxorubicin