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.
Highlights
The leading causes of death in the world have changed from accidental or infectious diseases to cancer
All of the results indicated that Hep88 monoclonal antibodies (mAbs) induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases
Our preliminary studies showed that Hep88 mAb has tumoricidal activity against the Hepatocellular carcinoma (HCC) (HepG2 cell line), while harmless to the normal liver cell line (Chang liver) (Puthong et al, 2009)
Summary
The leading causes of death in the world have changed from accidental or infectious diseases to cancer. The main etiology for HCC in Thailand is hepatitis B virus (HBV) infection, while, worldwide, the dominant etiologies are chronic infection of hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol and aflatoxin ingestion. These agents alter the function of groups of genes involved in the control of cell growth, apoptosis and DNA repair. The technologies in HCC treatment and diagnosis have been continuously developed, the incidence of HCC and the mortality rate of HCC patients are still increasing annually This trend results from defects in sensitivity and specificity during early detection, as well as less effective treatment in eliminating any remaining cancer cells
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