title: Hep88 mAb-mediated paraptosis-like apoptosis in HepG2 cells via downstream upregulation and activation of caspase-3, caspase-8 and caspase-9.
abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Presently, targeted therapy via monoclonal antibodies to specific tumor-associated antigens is being continuously developed. Hep88 mAb has proven to exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To verify the pathway, we then demonstrated downstream up-regulation of caspase-3, caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated enzyme activity by colorimetric assay. Active caspase-3 determination was also accomplished by flow cytometry. Active caspase-3 expression was increased by Hep88 mAb treatment in a dose-and time-dependent manner. All of the results indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases. These conclusions imply that Hep88mAb might be a promising tool for the effective treatment of HCC in the future.
authors.affiliation: Faculty of Medicine, Thammasat University (Rangsit Campus), Pathum Thani, Thailand E-mail : panadda_rojpibulstit@hotmail.com.
authors.forename: Thantip
authors.initials: T
authors.lastname: Mitupatum
authors.forename: Kalaya
authors.initials: K
authors.lastname: Aree
authors.forename: Suthathip
authors.initials: S
authors.lastname: Kittisenachai
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.forename: Songchan
authors.initials: S
authors.lastname: Puthong
authors.forename: Sasichai
authors.initials: S
authors.lastname: Kangsadalampai
authors.forename: Panadda
authors.initials: P
authors.lastname: Rojpibulstit
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D053181:Caspase 8 / Q000096:biosynthesis / Q000235:genetics; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D004317:Doxorubicin; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9