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 Lam, Hsing-Jien Kung

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere70910
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 15 2013

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prostatic neoplasms
Prostatic Neoplasms
apoptosis
Cells
Apoptosis
Protein-Tyrosine Kinases
metastasis
tyrosine
phosphotransferases (kinases)
Neoplasm Metastasis
src-Family Kinases
autophagy
neoplasm cells
2-(dibenzo(b,d)furan-2-yl)-7-phenyl-1-(3-(piperidin-1-yl)propyl)-1H-imidazo(4,5-g)quinoxalin-6(5H)-one
Human Umbilical Vein Endothelial Cells
Autophagy
drug resistance
angiogenesis
tissue repair
Drug Resistance

ASJC Scopus subject areas

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

Cite this

CTA095, a Novel Etk and Src Dual Inhibitor, Induces Apoptosis in Prostate Cancer Cells and Overcomes Resistance to Src Inhibitors. / Guo, Wenchang; Liu, Ruiwu; Bhardwaj, Gaurav; Ma, Ai Hong; Changou, Chun; Yang, Joy C.; Li, Yuanpei; Feng, Caihong; Luo, Yan; Mazloom, Anisha; Sanchez, Eduardo; Wang, Yan; Huang, Wenzhe; Patterson, Randen; Evans, Christopher P; Lam, Kit; Kung, Hsing-Jien.

In: PLoS One, Vol. 8, No. 8, e70910, 15.08.2013.

Research output: Contribution to journalArticle

Guo, W, Liu, R, Bhardwaj, G, Ma, AH, Changou, C, Yang, JC, Li, Y, Feng, C, Luo, Y, Mazloom, A, Sanchez, E, Wang, Y, Huang, W, Patterson, R, Evans, CP, Lam, K & Kung, H-J 2013, 'CTA095, a Novel Etk and Src Dual Inhibitor, Induces Apoptosis in Prostate Cancer Cells and Overcomes Resistance to Src Inhibitors', PLoS One, vol. 8, no. 8, e70910. https://doi.org/10.1371/journal.pone.0070910
Guo, Wenchang ; Liu, Ruiwu ; Bhardwaj, Gaurav ; Ma, Ai Hong ; Changou, Chun ; Yang, Joy C. ; Li, Yuanpei ; Feng, Caihong ; Luo, Yan ; Mazloom, Anisha ; Sanchez, Eduardo ; Wang, Yan ; Huang, Wenzhe ; Patterson, Randen ; Evans, Christopher P ; Lam, Kit ; Kung, Hsing-Jien. / CTA095, a Novel Etk and Src Dual Inhibitor, Induces Apoptosis in Prostate Cancer Cells and Overcomes Resistance to Src Inhibitors. In: PLoS One. 2013 ; Vol. 8, No. 8.
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