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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 a ndrogen synthesis, 2 HF 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.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalOncology Reports
Volume32
Issue number1
DOIs
StatePublished - 2014

Fingerprint

STAT3 Transcription Factor
Prostate
Prostatic Neoplasms
Apoptosis
Castration
Growth
Neoplasms
Phosphorylation
Therapeutic Uses
Caspases
Flavonoids
Transcriptional Activation
Androgens
2'-hydroxyflavanone
Cell Proliferation
Survival
Therapeutics

Keywords

  • 2′-hydroxyflavanone
  • AKT
  • Cell apoptosis
  • Prostate cancer
  • STAT3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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.

In: Oncology Reports, Vol. 32, No. 1, 2014, p. 131-138.

Research output: Contribution to journalArticle

Wu, Kaijie ; Ning, Zhongyun ; Zhou, Jiancheng ; Wang, Bin ; Fan, Jinhai ; Zhu, Jianning ; Gao, Yang ; Wang, Xinyang ; Hsieh, Jer Tsong ; He, Dalin. / 2′-Hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis. In: Oncology Reports. 2014 ; Vol. 32, No. 1. pp. 131-138.
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