CTA095, a Novel Etk and Src Dual Inhibitor, Induces Apoptosis in Prostate Cancer Cells and Overcomes Resistance to Src Inhibitors

Wenchang Guo, Ruiwu Liu, Gaurav Bhardwaj, Ai Hong Ma, Chun Changou, Joy C. Yang, Yuanpei Li, Caihong Feng, Yan Luo, Anisha Mazloom, Eduardo Sanchez, Yan Wang, Wenzhe Huang, Randen Patterson, Christopher P. Evans, Kit S. Lam, Hsing Jien Kung

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6 引文 斯高帕斯(Scopus)

摘要

Etk is a non-receptor tyrosine kinase, which provides a strong survival signal in human prostate cancer cells. Src, another tyrosine kinase that cross-activates with Etk, has been shown to play an important role in prostate cancer metastasis. Herein, we discovered a new class of Etk inhibitors. Within those inhibitors, CTA095 was identified as a potent Etk and Src dual inhibitor. CTA095 was found to induce autophagy as well as apoptosis in human prostate cancer cells. In addition, CTA095 inhibited HUVEC cell tube formation and "wound healing" of human prostate cancer cells, implying its role in inhibition of angiogenesis and metastasis of human prostate cancer. More interestingly, CTA095 could overcome Src inhibitor resistance in prostate cancer cells. It induces apoptosis in Src inhibitor resistant prostate cancer cells, likely through a mechanism of down regulation of Myc and BCL2. This finding indicates that simultaneously targeting Etk and Src could be a promising approach to overcome drug resistance in prostate cancer.
原文英語
文章編號e70910
期刊PLoS One
8
發行號8
DOIs
出版狀態已發佈 - 八月 15 2013
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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