November 2013 – 'Pao pereira Extract Suppresses Castration- Resistant Prostate Cancer Cell Growth, Survival and Invasion Through Inhibition of NFkB Signaling'
by Cunjie Chang, BS, Wei Zhao, MS, Bingxian Xie, BS, Yongming Deng, BS, Tao Han, BM, Yangyan Cui, BS, Yundong Dai, BS, Zhen Zhang, BS, Jimin Gao, MD, PhD, Hongqian Guo, MD, PhD, and Jun Yan, PhD.
Integr Cancer Ther. 2014 May;13(3):249-58. Doi: 10.1177/1534735413510557. Epub 2013 Nov 27
Dr. Jun Yan from Dr. Aaron Katz's laboratory at Columbia University Medical Center is continuing research (University of Nanjing, China) on the anti-cancer and anti-inflammatory activities of Pao Pereira (extract provided by Natural Source International, Ltd.).
Dr. Jun Yan uses up to date techniques to determine how the Pao pereira extract exerts its effects, what molecules it influences in the cell and what responses are triggered. The publication shows that this Pao pereira extract is effective against prostate cancer cells that no longer respond to agents that interfere with hormone action.
Such drugs are specifically designed to limit the effects of testosterone, the male hormone that stimulates the growth of prostate cancer cells. Over time, prostate tumors become resistant to these anti-hormones indicting that the cancer has become more aggressive. The study shows that these hormone independent prostate cancer cells are susceptible to the growth inhibition of Pao pereira as are prostate cancers that still respond to testosterone. The study also revealed that Pao pereira acts on a signaling complex called NFkB—a control center regulating cell survival, proliferation, and invasion. The results suggest that Pao pereira will be useful for men with advanced hormone-independent prostate cancer.
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.