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Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling.
Integr Cancer Ther. 2014 May; 13(3):249-58.IC

Abstract

Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose- and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL, and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NFκB/p65, NFκB DNA binding activity, and luciferase reporter activity. Pao inhibited TNFα-induced relocation of NFκB/p65 to the nucleus, NFκB/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NFκB/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-xL, and XIAP), and metastasis (VEGFa, MMP9, and GROα/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NFκB/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NFκB activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC.

Authors+Show Affiliations

Nanjing University, Nanjing, China.Nanjing University, Nanjing, China.Nanjing University, Nanjing, China.Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.Nanjing University, Nanjing, China.Wenzhou Medical College, Wenzhou, China.Wenzhou Medical College, Wenzhou, China.Wenzhou Medical College, Wenzhou, China.Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.Nanjing University, Nanjing, China Wenzhou Medical College, Wenzhou, China yanjun@nju.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24287876

Citation

Chang, Cunjie, et al. "Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling." Integrative Cancer Therapies, vol. 13, no. 3, 2014, pp. 249-58.
Chang C, Zhao W, Xie B, et al. Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling. Integr Cancer Ther. 2014;13(3):249-58.
Chang, C., Zhao, W., Xie, B., Deng, Y., Han, T., Cui, Y., Dai, Y., Zhang, Z., Gao, J., Guo, H., & Yan, J. (2014). Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling. Integrative Cancer Therapies, 13(3), 249-58. https://doi.org/10.1177/1534735413510557
Chang C, et al. Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling. Integr Cancer Ther. 2014;13(3):249-58. PubMed PMID: 24287876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling. AU - Chang,Cunjie, AU - Zhao,Wei, AU - Xie,Bingxian, AU - Deng,Yongming, AU - Han,Tao, AU - Cui,Yangyan, AU - Dai,Yundong, AU - Zhang,Zhen, AU - Gao,Jimin, AU - Guo,Hongqian, AU - Yan,Jun, Y1 - 2013/11/27/ PY - 2013/11/30/entrez PY - 2013/11/30/pubmed PY - 2016/12/15/medline KW - NFκB signal pathway KW - Pao extract KW - apoptosis KW - castration-resistant prostate cancer KW - cell growth arrest KW - herbal medicine SP - 249 EP - 58 JF - Integrative cancer therapies JO - Integr Cancer Ther VL - 13 IS - 3 N2 - Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose- and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL, and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NFκB/p65, NFκB DNA binding activity, and luciferase reporter activity. Pao inhibited TNFα-induced relocation of NFκB/p65 to the nucleus, NFκB/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NFκB/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-xL, and XIAP), and metastasis (VEGFa, MMP9, and GROα/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NFκB/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NFκB activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC. SN - 1552-695X UR - https://www.unboundmedicine.com/medline/citation/24287876/Pao_Pereira_Extract_Suppresses_Castration_Resistant_Prostate_Cancer_Cell_Growth_Survival_and_Invasion_Through_Inhibition_of_NFκB_Signaling_ L2 - https://journals.sagepub.com/doi/10.1177/1534735413510557?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -