Open AccessDevelopment of a novel prostate apoptosis response-4 (Par-4) protein entity with an extended duration of action for therapeutic treatment of cancer
Author(s) -
KyungBo Kim,
Nathália Araujo,
Nikhil Hebbar,
Ziyuan Zhou,
Xirong Zheng,
Fang Zheng,
Vivek M. Rangnekar,
ChangGuo Zhan
Publication year - 2019
Publication title -
protein engineering, design and selection
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.627
H-Index - 109
eISSN - 1741-0134
pISSN - 1741-0126
DOI - 10.1093/protein/gzz034
Subject(s) - in vivo , apoptosis , prostate cancer , cancer research , cancer , prostate , suppressor , biology , in vitro , function (biology) , chemistry , microbiology and biotechnology , biochemistry , genetics
Prostate apoptosis response-4 (Par-4) is a tumor suppressor which protects against neoplastic transformation. Remarkably, Par-4 is capable of inducing apoptosis selectively in cancer cells without affecting the normal cells. In this study, we found that recombinant Par-4 protein had limited serum persistence in mice that may diminish its anti-tumor activity in vivo. To improve the in vivo performance of the short-lived Par-4 protein, we aimed to develop a novel, long-lasting form of Par-4 with extended sequence, denoted as Par-4Ex, without affecting the desirable molecular function of the natural Par-4. We demonstrate that the Par-4Ex protein entity, produced by using the Escherichia coli expression system suitable for large-scale production, fully retains the desirable pro-apoptotic activity of Par-4 protein, but with ~7-fold improved biological half-life. Further in vivo tests confirmed that, due to the prolonged biological half-life, the Par-4Ex protein is indeed more potent in suppressing metastatic tumor growth in mice.