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

Abstract

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.

Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR)

“…Similarly, baicalein has been reported to have an inhibitory effect on ERK1/2 phosphorylation in both in vivo and in vitro (Agarwal et al, 2009;Gao et al, 2013;Chen et al, 2013;Liang et al, 2012;Zhou et al, 2013). On the other hand opposite effects have also been reported for baicalein, baicalin and galangin, suggesting cellor tissue-specific effects (Chen et al, 2006;Lei et al, 2012;Liu et al, 2013;Zhou et al, 2009). These data together with the recent findings of the research group of Dr. Masahiko Negishi defining the indirect activation of CAR via EGFR inhibition (Mutoh et al, 2013) urge for a comprehensive study of the molecular mechanism of their interactions with CAR.…”

Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes

“…p38 is usually activated by inflammatory cytokines and leads to cell apoptosis [16,18] . Interestingly, several recent papers revealed different data about the activation of ERK or p38 in the CD151 signaling path way [6,7,26] .…”

“…Hence, a "transmembrane linker" model for CD151 has been proposed, and CD151 signaling is thought to be mediated by CD151-integrin complexes [6,14,15] . Mitogen-activated protein (MAP) kinases play important roles in various cellular responses [16][17][18] . In this study, using a gene transfer technique with a recombinant adeno-associated virus (rAAV) vector, we examined the roles of MAP kinases, particularly extracellular signal-regulated kinase (ERK) and p38 MAP kinase (p38), in CD151-induced endothelial cell proliferation, migration and tube formation.…”

In vitro and in vivo evaluation of the genotoxicity of Gumiganghwal-tang, a traditional herbal prescription

“…Liquiritin confers neuroprotective effects against focal cerebral ischemia/reperfusion in mice via its antioxidant and antiapoptosis properties (Sun et al, 2010). Baicalin and baicalein confer anticancer properties via the ERK/p38 MAPK pathway in human breast cancer cells (Zhou et al, 2009). The anti-inflammatory effects of ferulic acid (Huang et al, 2011) and glycyrrhizin (Kudo et al, 2011) were also reported.…”