title: Kuguacin J, a triterpeniod from Momordica charantia leaf, modulates the progression of androgen-independent human prostate cancer cell line, PC3.
abstract: 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.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Wilart
authors.initials: W
authors.lastname: Pompimon
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Pornngarm
authors.initials: P
authors.lastname: Limtrakul
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D029775:Momordica / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014315:Triterpenes / Q000032:analysis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000728:Androgens; D017931:DNA Primers; D012333:RNA, Messenger; D014315:Triterpenes; C572783:kuguacin J; D020782:Matrix Metalloproteinases