2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis

Wu,Kaijie; Ning,Zhongyun; Zhou,Jiancheng; Wang,Bin; Fan,Jinhai; Zhu,Jianning; Gao,Yang; Wang,Xinyang; Hsieh,Jer-Tsong; He,Dalin

doi:10.3892/or.2014.3218

2'-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis

Authors:
- Kaijie Wu
- Zhongyun Ning
- Jiancheng Zhou
- Bin Wang
- Jinhai Fan
- Jianning Zhu
- Yang Gao
- Xinyang Wang
- Jer-Tsong Hsieh
- Dalin He
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Affiliations: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Published online on: May 26, 2014 https://doi.org/10.3892/or.2014.3218
Pages: 131-138

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Abstract

Although there have been advances in therapeutic regimes for metastatic castration-resistant prostate cancer (CRPC), these recent developments have not led to improved cure rates. Thus, more novel agents to prolong patient survival are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth and its potential mechanisms in CRPC have not been completely elucidated. In the present study, utilizing three different metastatic and androgen-independent PCa cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted in inhibition of cell proliferation and colony formation in vitro, but also delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known inhibitory effects on aldo‑keto reductase activity and de novo androgen synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer and activator of transcription-3 (STAT3) phosphorylation and transactivation subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl-1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.

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