Hep 88 mAB induced ultrastructural alteration through apoptosis like program cell death in hepatocellular carcinoma.

Hep88 mAbs, a novel monoclonal antibodies against hepatocellular carcinoma cell line from Thai patient, has been proved earlier for its tumoricidal effect on HepG2 cell line. In the present study, we investigated not only Hep88 mAb's targeted proteins from HepG2 cell line by western blot analysis but also its inhibitory activity on those cells by MTT assay. Moreover the ultrastructural alteration induced by Hep88 mAb of HepG2 cell line compare with Chang liver cell line was also examined. The results demonstrated that Hep88 mAb had cytotoxic effect on HepG2 cell line but not Chang liver cell line. Additionally, recognizing proteins against Hep88 mAb have been found on both cell lines. The ultrastructural alteration detected from transmission electron microscopy included the appearing of intracellular vacuolization as well as the dilatation of endoplasmic reticulum and mitochondria have been observed. These findings are suggested that the death of HepG2 cell line after treatment with Hep88 mAb might be involved by an apoptosis-like program cell death (PCD) pathway. From all of these remarks, it is possible that Hep88 mAb can injure HCC cells by binding with its membrane-bound antigen and activated downstream intracellular signals which is finally leading cell to be death via apoptosis-like PCD.

Secreted Opisthorchis viverrini glutathione S-transferase regulates cell proliferation through AKT and ERK pathways in cholangiocarcinoma.

Opisthorchis viverrini can develop mitogenic substances into the excretory/secretory product (ESP) that may play an important role in promoting the genesis of cholangiocarcinoma (CCA). In the present study, glutathione S-transferase (GST) is identified as being secreted into Ov-ESP and acting as one of the parasitic mitogens. Its proliferative effect and possible mechanism were explored and its association with the tumor development is proposed. Ov-ESP was concentrated and purified by gel filtration chromatography. SDS-PAGE, 2-DE, and LC-MS/MS identified GST predominantly expressed in the proliferative ESP fraction. The recombinant OvGST (rOvGST) was produced by wheat germ cell-free expression and confirmed by an MTS assay to have a proliferative function on NIH-3T3 murine fibroblasts and MMNK1 non-tumorigenic human bile duct epithelial cells in a dose dependent manner with different optimal doses. The cell surface binding of rOvGST was confirmed in vitro and the activation of both pAKT and pERK was revealed as the mechanism of OvGST-mediated cell proliferation. With support from the observation of secreted OvGST on the biliary cells surrounding the parasites, it is suggested that OvGST can promote cell proliferation that consequently may accelerate the genesis of CCA.