The genetically engineered drug rhCNB induces apoptosis via a mitochondrial route in tumor cells
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Yang Yang1,*, Huan Yang1,*, Jinju Yang1, Li Li1, Benqiong Xiang1 and Qun Wei1
1Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, People’s Republic of China
*These authors have contributed equally to this work
Qun Wei, email: firstname.lastname@example.org
Benqiong Xiang, email: Xiangbq@bnu.edu.cn
Keywords: rhCNB, mitochondrial apoptosis, Bcl-2 family, tumor targeting, anti-tumor drug
Received: November 30, 2016 Accepted: June 27, 2017 Published: July 22, 2017
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.
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