The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells  

作　　者：Qian-mei ZHOU Song WANG Hui ZHANG Yi-yu LU Xiu-feng WANG Yoshiharu MOTOO Shi-bing SU 

机构地区：[1]Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [2]Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293 Japan

出　　处：《Acta Pharmacologica Sinica》2009年第12期1648-1658,共11页中国药理学报（英文版）

摘　　要：Aim： To examine whether the cell growth inhibitory effect of the combination of baicalin and baicalein is related to apoptosis. Moreover, to determine whether the expression of some apoptosis-related proteins is regulated by the ERK/p38 MAPK pathway. Methods： Cell viability was measured using a 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Apoptosis was detected by acridine orange （AO） staining, DNA ladder assay and flow cytometric analysis. Apoptosis-related proteins were observed using Western blot analysis. Results： Compared with baicalin or baicalein alone, the combination treatment of baicalin （50 μmol/L） and baicalein （25 μmol/L） had an anti-proliferative effect in a time-dependent manner. Isobologram analysis demonstrated that the combination treatment had a synergistic effect. Moreover, apoptosis in MCF-7 cells was increased by 12% and 20% with the combination treatment at 24 h and 48 h, respectively. With the combination treatment in MCF-7 cells, cleaved caspase-3 and caspase-9 were observed, and the level of bcl-2 expression was decreased approximately 20% and 40% at 24 h and 48 h, respectively. The expression of bax and p53 were increased about 25% and 15% at 48 h, respectively. Moreover, the activation of caspase-3, -9 and the regulation of bcl-2, bax and p53 were related to ERK/p38 MAPK activation. Conclusion： In this study, apoptosis was enhanced by the combination treatment of baicalin and baicalein, which activated caspases-3 and caspase-9, downregulated the level of bcl-2 and upregulated the level of bax or p53 via the ERK/p38 MAPK pathway.Aim： To examine whether the cell growth inhibitory effect of the combination of baicalin and baicalein is related to apoptosis. Moreover, to determine whether the expression of some apoptosis-related proteins is regulated by the ERK/p38 MAPK pathway. Methods： Cell viability was measured using a 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Apoptosis was detected by acridine orange （AO） staining, DNA ladder assay and flow cytometric analysis. Apoptosis-related proteins were observed using Western blot analysis. Results： Compared with baicalin or baicalein alone, the combination treatment of baicalin （50 μmol/L） and baicalein （25 μmol/L） had an anti-proliferative effect in a time-dependent manner. Isobologram analysis demonstrated that the combination treatment had a synergistic effect. Moreover, apoptosis in MCF-7 cells was increased by 12% and 20% with the combination treatment at 24 h and 48 h, respectively. With the combination treatment in MCF-7 cells, cleaved caspase-3 and caspase-9 were observed, and the level of bcl-2 expression was decreased approximately 20% and 40% at 24 h and 48 h, respectively. The expression of bax and p53 were increased about 25% and 15% at 48 h, respectively. Moreover, the activation of caspase-3, -9 and the regulation of bcl-2, bax and p53 were related to ERK/p38 MAPK activation. Conclusion： In this study, apoptosis was enhanced by the combination treatment of baicalin and baicalein, which activated caspases-3 and caspase-9, downregulated the level of bcl-2 and upregulated the level of bax or p53 via the ERK/p38 MAPK pathway.

关 键 词：BAICALIN BAICALEIN combination therapy APOPTOSIS breast cancer cells 

分 类 号：Q26[生物学—细胞生物学] Q255