Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells

Takahashi, Hiroki; Chen, Monica C; Pham, Hung; Angst, Eliane; King, Jonathan C; Park, Jenny; Brovman, Ethan Y; Ishiguro, Hideyuki; Harris, Diane M; Reber, Howard A; Hines, Oscar J; Gukovskaya, Anna S; Go, Vay Liang W; Eibl, Guido (2011). Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochimica et biophysica acta - molecular cell research, 1813(8), pp. 1465-74. New York, N.Y.: Elsevier 10.1016/j.bbamcr.2011.05.003

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Angst, Eliane

ISSN:

0167-4889

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

17 Mar 2015 20:59

Publisher DOI:

10.1016/j.bbamcr.2011.05.003

PubMed ID:

21596068

Web of Science ID:

000292945200009

URI:

https://boris.unibe.ch/id/eprint/7488 (FactScience: 212758)

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