Withdrawal NoticeThis paper was originally published in Oncotarget Advance Online Publications on 03/04/2019.
In compliance with Oncotarget's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Oncotarget internal or any external indexes or archives.
Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling
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
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
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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