Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells.
Berberine has anti-tumor properties in some cancer cells including prostate cancer, but the exact mechanisms and in vivo effects are unclear. We investigated anti-cancer activity of berberine in vitro and in vivo, and possible mechanisms in prostate cancer cells. Berberine treatment inhibited cell cancer growth in a concentration (0-50 microM) and time- (0-48 h) dependent manner without any growth inhibition in normal human prostate epithelial PWR-1E cells. However, the p53 expressing LNCaP cells were more susceptible against berberine than the p53 lacking PC-3 cells. The cell arrest in G0/G1 phase, apoptotic cell death and the expression of apoptotic cell death proteins Bax and caspase-3 was much higher in berberine-treated LNCaP cells than those in PC-3 cells. Exploration of p53 siRNA or pifithrin-alpha, a p53 inhibitor to the LNCaP cells, suppressed berberine-induced cell death and expression of apoptosis-related proteins. In xenograft in vivo studies, berberine reduced tumor weights and volumes accompanied with apoptotic cell death and increased expression of apoptotic cell death proteins, however, the extent of inhibitory effect was more significant in LNCaP cell-bearing mice. Therefore, these results indicated that berberine inhibited p53-dependent prostate cancer cell death.
College of Pharmacy and MRC, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.
Myoung Suk
MS
Choi
Ju Hoon
JH
Oh
Sun Mi
SM
Kim
Hai Young
HY
Jung
Hwan Soo
HS
Yoo
Yong Moon
YM
Lee
Dong Cheul
DC
Moon
Sang Bae
SB
Han
Jin Tae
JT
Hong
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D001599:Berberine