The genetically engineered drug rhCNB induces apoptosis via a mitochondrial route in tumor cells.

The genetically engineered drug rhCNB induces apoptosis via a mitochondrial route in tumor cells. Oncotarget. 2017 Jul 22;: Authors: Yang Y, Yang H, Yang J, Li L, Xiang B, Wei Q Abstract The calcineurin B subunit (CNB) has antitumor activity. We showed previously that recombinant human CNB (rhCNB) also had strong anti-tumor activity in vivo, and was thus a promising candidate anti-tumor drug. It appeared to kill tumor cells via immunomodulation. Here, we show that rhCNB inhibits the proliferation of human hepatoma HepG-2 cells, resulting in their apoptosis. Exogenous CNB was found to localize to mitochondria in tumor cells and activate the mitochondrial apoptosis pathway, as indicated by a decrease of mitochondrial transmembrane potential, release of cytochrome C and activation of caspase-9, which then activates caspase-3. At the same time Bcl-2 &Bcl-xL expression decreased, Bim expression increased, and Bax was activated. Interaction between rhCNB and Bcl-xL was detected, which may inhibit the function of Bcl-xL. Long-term tumor targeting was also observed in nude mice. These data deepened our understanding of the anti-tumor mechanism of rhCNB and provided guidance for its drug development. PMID: 28779065 [PubMed - as supplied by publisher]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research