Kuguacin J, a triterpeniod from Momordica charantia leaf, modulates the progression of androgen-independent human prostate cancer cell line, PC3

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• 作者：Pornsiri Pitchakarn^a ; ^d ; Shugo Suzuki^a ; ^{shugo@med.nagoya-cu.ac.jp} ; Kumiko Ogawa^a ; ^b ; Wilart Pompimon^c ; Satoru Takahashi^a ; Makoto Asamoto^a ; Pornngarm Limtrakul^d ; ^{plimtrak@med.cmu.ac.th} ; Tomoyuki Shirai^a
• 关键词：Prostate cancer ; Cell growth ; Invasion ; Bitter melon ; Kuguacin J
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：March-April, 2012
• 卷：50
• 期：3-4
• 页码：840-847
• 文件大小：838 K

摘要

In this study, we focused on the in vitro effects of Kuguacin J (KuJ), a purified component of bitter melon (Momordica charantia) leaf extract (BMLE), on the androgen-independent human prostate cancer cell line PC3 and the in vivo effect of dietary BMLE on prostate carcinogenesis using a PC3-xenograph model. KuJ exerted a strong growth-inhibitory effect on PC3 cells. Growth inhibition was mainly through G1-arrest: KuJ markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (Cdk2 and Cdk4) and proliferating cell nuclear antigen. Interestingly, KuJ also dramatically decreased the levels of survivin expressed by PC3 cells. In addition, KuJ exerted anti-invasive effects on PC3 cells, significantly inhibiting migration and invasion: KuJ inhibited secretion of the active forms of MMP-2, MMP-9 and uPA by PC3 cells. In addition, KuJ treatment significantly decreased the expression of membrane type 1-MMP (MT1-MMP) by PC3 cells. In vivo, 1%and 5%BMLE in the diet resulted in 63%and 57%inhibition of PC3 xenograft growth without adverse effect on host body weight. Our results suggest that KuJ is a promising new candidate chemopreventive and chemotherapeutic agent for prostate cancer.