title: Retracted: Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling.
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.
authors: Department of Urology, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA.
authors: Yajuan
authors: Y
authors: Gao
authors: University of Pittsburgh Cancer Institute, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA.
authors: Yan
authors: Y
authors: Zeng
authors: Department of Urology, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA.
authors: Jian
authors: J
authors: Tian
authors: Department of Urology, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA.
authors: Mohammad Shyful
authors: MS
authors: Islam
authors: Department of General Surgery, the 2nd Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors: Guoqin
authors: G
authors: Jiang
authors: Department of Urology, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA. University of Pittsburgh Cancer Institute, University of Pittsburgh Medical College, University of Pittsburgh, Shadyside Medical Center, Pittsburgh, PA, USA.
authors: Dong
authors: D
authors: Xiao
mesh_terms: D006801:Humans; D008297:Male; D011282:Pregnenediones; D011471:Prostatic Neoplasms
chemical_list: D011282:Pregnenediones; C023617:pregna-4,17-diene-3,16-dione