Isoliquiritigenin inhibits the growth of prostate cancer.
OBJECTIVE
Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro.


METHODS
DU145 and LNCaP prostate cancer cell lines were used as targets. We examined the effects of isoliquiritigenin on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the effects of isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter activity.


RESULTS
Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner. Fluorescence-activated cell sorting (FACS) analysis indicated that isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced the expression of GADD153 mRNA and protein associated with cell cycle arrest. Further, isoliquiritigenin stimulated transcriptional activity of GADD153 promoter dose-dependently.


CONCLUSIONS
These findings suggest that isoliquiritigenin is a candidate agent for the treatment of prostate cancer and GADD153 may play an important role in isoliquiritigenin-induced cell cycle arrest and cell growth inhibition.
Kanazawa
Motohiro
M
Department of Urology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. motohiro@koto.kpu-m.ac.jp
Satomi
Yoshiko
Y
Mizutani
Yoichi
Y
Ukimura
Osamu
O
Kawauchi
Akihiro
A
Sakai
Toshiyuki
T
Baba
Masaki
M
Okuyama
Toru
T
Nishino
Hoyoku
H
Miki
Tsuneharu
T
D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006035:Glycyrrhiza; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D022762:CCAAT-Enhancer-Binding Proteins; D047188:Chalcones; C497249:DDIT3 protein, human; D005419:Flavonoids; D010936:Plant Extracts; D012333:RNA, Messenger; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D002599:Chalcone; C040920:isoliquiritigenin