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http://dx.doi.org/10.7314/APJCP.2015.16.5.1771

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))
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.5, 2015 , pp. 1771-1779 More about this Journal
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;
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