title: Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling.
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.affiliation: Nanjing University, Nanjing, China.
authors.forename: Cunjie
authors.initials: C
authors.lastname: Chang
authors.affiliation: Nanjing University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Nanjing University, Nanjing, China.
authors.forename: Bingxian
authors.initials: B
authors.lastname: Xie
authors.affiliation: Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Nanjing University, Nanjing, China.
authors.forename: Yangyan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Wenzhou Medical College, Wenzhou, China.
authors.forename: Yundong
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Wenzhou Medical College, Wenzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Wenzhou Medical College, Wenzhou, China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Nanjing Urology Research Center, Nanjing, China.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Guo
authors.affiliation: Nanjing University, Nanjing, China Wenzhou Medical College, Wenzhou, China yanjun@nju.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013020:South America; D013997:Time Factors; D014197:Trees / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts
keywords: NFκB signal pathway; Pao extract; apoptosis; castration-resistant prostate cancer; cell growth arrest; herbal medicine