title: Baicalein Induces Beclin 1- and Extracellular Signal-Regulated Kinase-Dependent Autophagy in Ovarian Cancer Cells.
abstract: Baicalein (BA), one of the major compounds isolated from the root of Scutellaria baicalensis Gerogi, exhibits various pharmacological effects, such as anti-oxidant, anti-inflammatory, and anticancer effects. In this study, we found that BA reduced cell viability and increased apoptosis in ovarian cancer cells. Treatment of cells with BA enhanced microtubule-associated protein light chain 3-II (LC3-II) expression, acidic vesicular organelle and GFP-LC3 fluorescence dot accumulation. Combined treatment with chloroquine and BA apparently reduced cell viability and increased the cleavage of poly (ADPribose) polymerase (PARP) in both HEY and A2780 ovarian cancer cell lines, indicating that BA induces a protective autophagy in these cells. Knockdown of Beclin 1 by siRNA remarkably decreased BA-induced LC3-II lipidation. In addition, we found an increase in the phosphorylation of extracellular signal-regulated kinase (ERK, Thr202/Thr204) and AKT (Ser473) after BA treatment, and inhibition of ERK activation by the pharmacological inhibitor U0126 or ERK siRNA blocked BA-induced autophagy. Taken together, these results suggest that BA induces Beclin 1- and ERK-dependent autophagy in ovarian cancer cells.
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Wang
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Yu-Lian
authors.initials: YL
authors.lastname: Xu
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Le-Le
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Lu
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
authors.affiliation: † Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, P.R. China.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: ‡ Department of Obstetrics and Gynecology-Division of Reproductive Science in Medicine, Department of Pathology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Wen-An
authors.initials: WA
authors.lastname: Qiang
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
authors.affiliation: * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000378:metabolism; D010051:Ovarian Neoplasms; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: D000962:Antimalarials; C491997:BECN1 protein, human; D000071186:Beclin-1; D004791:Enzyme Inhibitors; D044950:Flavanones; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C006680:baicalein; D002738:Chloroquine; D011065:Poly(ADP-ribose) Polymerases
keywords: Autophagy; Baicalein; Beclin1; ERK; Ovarian Cancer