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Unexpected heat shock element binding ability and tumor-killing activity of the combinatorial function domain of apoptin

Zhang, Liqiu; Yang, Jia; Liu, Lu; Tian, Wei; Gao, Ming; Song, Weiwei; Ling, Hong; Dong, Xingli

doi: 10.1097/CAD.0000000000000471
PRECLINICAL REPORTS
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Apoptin, derived from the chicken anemia virus, has been found to exert tumor-preferential apoptotic activity. It is a potential anticancer agent with direct clinical applications. However, if this viral protein were to be used as a new drug, it might also induce a strong immune response, causing toxic side effects. In a previous study, our group showed that TAT-apoptin downregulates the stress expression of heat shock protein 70 by competing with heat shock factor protein 1 in binding to the heat shock element (HSE) of the promoter region of heat shock protein 70, thus inducing specific apoptosis in HepG2 cells. In this study, we investigated the HSE-binding properties of the minimal functional region of apoptin. We showed that apoptin’s nuclear localization signals 1 and nuclear localization signals 2 represented functional regions that could bind with HSE and that this binding capacity was increased by polymers formed through the introduction of a leucine-rich stretch. Our data also showed that truncated combinatorial apoptin peptide has greater tumor-specific cell-killing activity and could be a potential antitumor agent.

aDepartment of Parasitology

bDepartment of Pharmacology

cDepartment of Biopharmaceutical Sciences, College of Pharmacy

dTeaching Experiment Center of Biotechnology, Harbin Medical University, Harbin, People’s Republic of China

Correspondence to Xingli Dong, PhD, Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang 150081, People’s Republic of China Tel: +86 451 866 60316; fax: +86 451 866 75769; e-mail: dongxingli@hotmail.com

Correspondence to Hong Ling, PhD, Department of Parasitology, Harbin Medical University,Baojian Road 157, Harbin, Heilongjiang 150081, People’s Republic of China Tel: +86 451 866 60316; fax: +86 451 866 75769; e-mail: lingh@ems.hrbmu.edu.cn

Received September 19, 2016

Accepted December 13, 2016

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