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Hep88 mAb-Mediated Paraptosis-Like Apoptosis in HepG2 Cells via Downstream Upregulation and Activation of Caspase-3, Caspase-8 and Caspase-9

  • Mitupatum, Thantip (Faculty of Medicine, Thammasat University (Rangsit Campus)) ;
  • Aree, Kalaya (Faculty of Medicine, Thammasat University (Rangsit Campus)) ;
  • Kittisenachai, Suthathip (Thailand National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park) ;
  • Roytrakul, Sittiruk (Thailand National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park) ;
  • Puthong, Songchan (Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering, Chulalongkorn University) ;
  • Kangsadalampai, Sasichai (Faculty of Medicine, Thammasat University (Rangsit Campus)) ;
  • Rojpibulstit, Panadda (Faculty of Medicine, Thammasat University (Rangsit Campus))
  • Published : 2015.03.18

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.

Keywords

Hepatocellular carcinoma;Hep88 monoclonal antibody;paraptosis;caspase

Acknowledgement

Supported by : Thammasat University

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