Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells

Shumin Zhang, Yanru Wang, Zhengjia Chen, Sungjin Kim, Shareen Iqbal, Andrew Chi, Chad Ritenour, Yongqiang A. Wang, Omer Kucuk, Daqing Wu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND. Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models. METHODS. The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models. RESULTS. Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis. CONCLUSION. This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC.

Original languageEnglish (US)
Pages (from-to)1681-1689
Number of pages9
JournalProstate
Volume73
Issue number15
DOIs
StatePublished - Nov 1 2013
Externally publishedYes

Fingerprint

Genistein
Castration
Prostatic Neoplasms
Drug Therapy
Theoretical Models
Apoptosis Regulatory Proteins
Isoflavones
cabazitaxel
Therapeutics
Luciferases
Heterografts
Apoptosis
Staining and Labeling
Growth

Keywords

  • cabazitaxel
  • chemoresistance
  • experimental model
  • genistein
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells. / Zhang, Shumin; Wang, Yanru; Chen, Zhengjia; Kim, Sungjin; Iqbal, Shareen; Chi, Andrew; Ritenour, Chad; Wang, Yongqiang A.; Kucuk, Omer; Wu, Daqing.

In: Prostate, Vol. 73, No. 15, 01.11.2013, p. 1681-1689.

Research output: Contribution to journalArticle

Zhang, S, Wang, Y, Chen, Z, Kim, S, Iqbal, S, Chi, A, Ritenour, C, Wang, YA, Kucuk, O & Wu, D 2013, 'Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells', Prostate, vol. 73, no. 15, pp. 1681-1689. https://doi.org/10.1002/pros.22705
Zhang, Shumin ; Wang, Yanru ; Chen, Zhengjia ; Kim, Sungjin ; Iqbal, Shareen ; Chi, Andrew ; Ritenour, Chad ; Wang, Yongqiang A. ; Kucuk, Omer ; Wu, Daqing. / Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells. In: Prostate. 2013 ; Vol. 73, No. 15. pp. 1681-1689.
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AB - BACKGROUND. Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models. METHODS. The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models. RESULTS. Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis. CONCLUSION. This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC.

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