Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells
Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells
复制标题
DOI：
10.1002/ijc.20588
复制
发表时间：
2005-03-10
影响因子：
6.4
通讯作者：
Simon, A
中科院分区：
文献类型：
--
作者：
Harmand, PO;Duval, R;Simon, A
未来几年，皮肤癌可能成为一个重大的公共卫生问题。先前的研究结果表明，熊果酸（UA）是一种五环三萜酸，具有多效性生物活性，例如对癌细胞的抗炎和抗增殖活性。由于 UA 是一种有前途的保护人类皮肤的化学实体，与化妆品行业所做的测试一致，我们研究了它对 M4Beu 人类黑色素瘤细胞系的影响。在本报告中，我们首次证明 UA 对 M4Beu 具有显着的抗增殖作用，并与诱导以 caspase-3 激活为特征的细胞凋亡过程相关。细胞凋亡的下游中枢效应子。我们证明，UA 诱导的细胞凋亡依赖于线粒体内在途径，如跨膜电位塌陷 (Deltapsim) 和 Bax-Bcl-2 平衡的改变所示，伴随着 Bax 表达的增加和 Bcl-2 表达的减少。我们还表明，UA 诱导的 Deltapsim 与线粒体中凋亡诱导因子的泄漏有关。综上所述，我们的结果表明，UA 诱导的 M4Beu 细胞凋亡是通过触发线粒体途径来完成的。总之，UA 可能是治疗或预防皮肤癌的一种令人鼓舞的化合物，并且可能代表一种治疗黑色素瘤的新的有前景的抗癌剂。 (C) 2004 年威利利斯。公司
Over the coming years, skin cancer could become a significant public health problem. Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid, has pleiotropic biologic activities such as antiinflammatory and antiproliferative activities on cancer cells. As UA represents a promising chemical entity for the protection of human skin, in agreement with tests done by the cosmetic industry, we investigated its effects on the M4Beu human melanoma cell line. In this report, we demonstrated for the first time that UA had a significant antiproliferative effect on M4Beu, associated with the induction of an apoptotic process, characterized by caspase-3 activation. the downstream central effector of apoptosis. We demonstrated that UA-induced apoptosis was dependent on the mitochondrial intrinsic pathway, as shown by transmembrane potential collapse (Deltapsim) and by alteration of the Bax-Bcl-2 balance, with a concomitant increase in Bax expression and decrease in Bcl-2 expression. We also showed that UA-induced Deltapsim was associated with apoptosis-inducing factor leakage from mitochondria. Taken together, our results suggest that UA-induced apoptosis on M4Beu cells is accomplished via triggering of mitochondrial pathway. In conclusion, UA could be an encouraging compound in the treatment or prevention of skin cancer and may represent a new promising anticancer agent in the treatment of melanoma. (C) 2004 Wiley-Liss. Inc.