Oncotarget. 2017 Jul 22;8(39):65876-65888. doi: 10.18632/oncotarget.19507. eCollection 2017 Sep 12.

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

Yang Y1, Yang H1, Yang J1, Li L1, Xiang B1, Wei Q1.

Author information

1Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, People’s Republic of China.

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.

KEYWORDS:

Bcl-2 family; anti-tumor drug; mitochondrial apoptosis; rhCNB; tumor targeting

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