title: 2'-hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis.
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.
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhongyun
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Urology, First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C520534:2'-hydroxyflavanone; D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt