title: Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells.
abstract: Scutellaria 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.
authors: Department of Surgery, UCLA Center for Excellence in Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Hiroki
authors: H
authors: Takahashi
authors: Monica C
authors: MC
authors: Chen
authors: Hung
authors: H
authors: Pham
authors: Eliane
authors: E
authors: Angst
authors: Jonathan C
authors: JC
authors: King
authors: Jenny
authors: J
authors: Park
authors: Ethan Y
authors: EY
authors: Brovman
authors: Hideyuki
authors: H
authors: Ishiguro
authors: Diane M
authors: DM
authors: Harris
authors: Howard A
authors: HA
authors: Reber
authors: Oscar J
authors: OJ
authors: Hines
authors: Anna S
authors: AS
authors: Gukovskaya
authors: Vay Liang W
authors: VL
authors: Go
authors: Guido
authors: G
authors: Eibl
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