Takahashi, HirokiHirokiTakahashiChen, Monica CMonica CChenPham, HungHungPhamAngst, ElianeElianeAngst0000-0003-4195-4399King, Jonathan CJonathan CKingPark, JennyJennyParkBrovman, Ethan YEthan YBrovmanIshiguro, HideyukiHideyukiIshiguroHarris, Diane MDiane MHarrisReber, Howard AHoward AReberHines, Oscar JOscar JHinesGukovskaya, Anna SAnna SGukovskayaGo, Vay Liang WVay Liang WGoEibl, GuidoGuidoEibl2024-10-112024-10-112011https://boris-portal.unibe.ch/handle/20.500.12422/77940Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.enarticle2159606800029294520000910.1016/j.bbamcr.2011.05.003