Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling

Yajuan Gao; Yan Zeng; Jian Tian; Mohammad Shyful Islam; Guoqin Jiang; Dong Xiao

doi:10.18632/oncotarget.2138

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This article has been retracted. Retraction in: https://doi.org/10.18632/oncotarget.6005

Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling

Yajuan Gao, Yan Zeng, Jian Tian, Mohammad Shyful Islam, Guoqin Jiang and Dong Xiao _

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Abstract

Yajuan Gao1, Yan Zeng2, Jian Tian1, Mohammad Shyful Islam1, Guoqin Jiang3 and Dong Xiao1,2

1 Department of Urology, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA

2 University of Pittsburgh Cancer Institute, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA

3 Department of General Surgery, the 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Correspondence:

Dong Xiao, email:

Keywords: Guggulsterone; prostate cancer; Apoptosis; Akt, ATP citrate lyase; xenografts

Received: April 24, 2014 Accepted: June 24, 2014 Published: June 26, 2014

Abstract

We have shown previously that Gugggulsterone (Gug) inhibits growth of cultured LNCaP and PC-3 human prostate cancer cells by causing apoptosis induction in association with reactive-oxygen species (ROS)-dependent activation of c-Jun N-terminal kinase (JNK). The present study builds upon the novel observations and now reveals a novel mechanism of Gug-anticancer activity that ATP citrate lyase (ACLY)-regulated Akt inactivation is involved in Gug-mediated inhibition of prostate cancer growth. Oral gavage of Gug significantly retarded the growth of PC-3 xenografts in athymic mice without causing weight loss and any other side effects. The Gug-induced apoptosis was associated with remarkably down-regulation of Akt and ACLY in both cancer cells and xenografts tumor tissue of Gug-treated group. Ectopic expression of constitutively active Akt conferred significant protection against Gug-mediated apoptotic cell death in both cancer cells. Moreover, the Gug-induced apoptosis, and Akt and ACLY inactivation in PC-3 and LNCaP cells was intensified by siRNA-based knockdown of ACLY protein level and by pharmacological inhibition of ACLY, or was protected by the ectopic expression of ACLY. In conclusion, the present study reveals a novel mechanism of Gug-anticancer activity that Gug-inhibited prostate cancer growth is regulated by ACLY/Akt signaling axis.

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Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling

Abstract