Choi Myoung Suk, Oh Ju Hoon, Kim Sun Mi, Jung Hai Young, Yoo Hwan Soo, Lee Yong Moon, Moon Dong Cheul, Han Sang Bae, Hong Jin Tae
College of Pharmacy and MRC, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.
Int J Oncol. 2009 May;34(5):1221-30.
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.
黄连素在包括前列腺癌在内的某些癌细胞中具有抗肿瘤特性，但其确切机制和体内效应尚不清楚。我们研究了黄连素在体外和体内的抗癌活性以及在前列腺癌细胞中的可能机制。黄连素处理以浓度（0 - 50微摩尔）和时间（0 - 48小时）依赖性方式抑制癌细胞生长，而对正常人前列腺上皮PWR - 1E细胞无任何生长抑制作用。然而，表达p53的LNCaP细胞比缺乏p53的PC - 3细胞对黄连素更敏感。黄连素处理的LNCaP细胞中G0/G1期细胞停滞、凋亡细胞死亡以及凋亡细胞死亡蛋白Bax和caspase - 3的表达均高于PC - 3细胞。对LNCaP细胞进行p53小干扰RNA或p53抑制剂pifithrin - α处理后，抑制了黄连素诱导的细胞死亡和凋亡相关蛋白的表达。在体内异种移植研究中，黄连素降低了肿瘤重量和体积，伴有凋亡细胞死亡以及凋亡细胞死亡蛋白表达增加，然而，在携带LNCaP细胞的小鼠中抑制作用的程度更为显著。因此，这些结果表明黄连素抑制p53依赖性前列腺癌细胞死亡。
