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

doi:10.1371/journal.pone.0070910

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 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 language	English
Article number	e70910
Journal	PLoS ONE
Volume	8
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0070910
Publication status	Published - 15 Aug 2013
Externally published	Yes

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Guo, W., Liu, R., Bhardwaj, G., Ma, A. H., Changou, C., Yang, J. C., Li, Y., Feng, C., Luo, Y., Mazloom, A., Sanchez, E., Wang, Y., Huang, W., Patterson, R., Evans, C. P., Lam, K. S., & 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, 8(8), Article e70910. https://doi.org/10.1371/journal.pone.0070910

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

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.",

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

year = "2013",

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doi = "10.1371/journal.pone.0070910",

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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, KS & Kung, HJ 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

TY - JOUR

T1 - CTA095, a Novel Etk and Src Dual Inhibitor, Induces Apoptosis in Prostate Cancer Cells and Overcomes Resistance to Src Inhibitors

AU - Guo, Wenchang

AU - Liu, Ruiwu

AU - Bhardwaj, Gaurav

AU - Ma, Ai Hong

AU - Changou, Chun

AU - Yang, Joy C.

AU - Li, Yuanpei

AU - Feng, Caihong

AU - Luo, Yan

AU - Mazloom, Anisha

AU - Sanchez, Eduardo

AU - Wang, Yan

AU - Huang, Wenzhe

AU - Patterson, Randen

AU - Evans, Christopher P.

AU - Lam, Kit S.

AU - Kung, Hsing Jien

PY - 2013/8/15

Y1 - 2013/8/15

N2 - 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.

AB - 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.

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DO - 10.1371/journal.pone.0070910

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AN - SCOPUS:84881581558

SN - 1932-6203

VL - 8

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e70910

ER -

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

Abstract

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