PMID- 19960010 OWN - NLM STAT- MEDLINE DCOM- 20100816 LR - 20220408 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 30 IP - 12 DP - 2009 Dec TI - The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells. PG - 1648-58 LID - 10.1038/aps.2009.166 [doi] AB - 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 micromol/L) and baicalein (25 micromol/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. FAU - Zhou, Qian-mei AU - Zhou QM AD - Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Wang, Song AU - Wang S FAU - Zhang, Hui AU - Zhang H FAU - Lu, Yi-yu AU - Lu YY FAU - Wang, Xiu-feng AU - Wang XF FAU - Motoo, Yoshiharu AU - Motoo Y FAU - Su, Shi-bing AU - Su SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 0 (Enzyme Inhibitors) RN - 0 (Flavanones) RN - 0 (Flavonoids) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (bcl-2-Associated X Protein) RN - 347Q89U4M5 (baicalin) RN - 49QAH60606 (baicalein) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - Apoptosis/*drug effects MH - Breast Neoplasms/drug therapy/pathology MH - Caspase 3/metabolism MH - Caspase 9/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Drug Synergism MH - Enzyme Inhibitors/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - Flavanones/*pharmacology MH - Flavonoids/*pharmacology MH - Humans MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Signal Transduction/*drug effects/physiology MH - Tumor Suppressor Protein p53/metabolism MH - bcl-2-Associated X Protein/metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism PMC - PMC4007493 EDAT- 2009/12/05 06:00 MHDA- 2010/08/17 06:00 PMCR- 2009/12/01 CRDT- 2009/12/05 06:00 PHST- 2009/12/05 06:00 [entrez] PHST- 2009/12/05 06:00 [pubmed] PHST- 2010/08/17 06:00 [medline] PHST- 2009/12/01 00:00 [pmc-release] AID - aps2009166 [pii] AID - 10.1038/aps.2009.166 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2009 Dec;30(12):1648-58. doi: 10.1038/aps.2009.166.