title: Opposite expression of securin and γ-H2AX regulates baicalein-induced cancer cell death.
abstract: Securin and γ-H2AX have been shown to regulate cell survival and genomic stability. However, it is still unknown how the expression and regulation of these proteins is altered following treatment with baicalein, a natural flavonoid extracted from the Scutellaria baicalensis root. In the present study, we investigate the possible roles of securin and γ-H2AX in baicalein-induced cancer cell death. Baicalein reduced cell viability in a variety of human cancer cell lines, including bladder, cervical, colon, and lung cancer cells. Interestingly, baicalein treatment (40-80 µM for 24 h) markedly inhibited securin expression, while the levels of γ-H2AX were elevated. Abnormal spindle formation and chromosomal segregation were induced by baicalein. Furthermore, wild type HCT116 cancer cells had a higher incidence of cytotoxicity and apoptosis than securin-null HCT116 cells following treatment with baicalein. In contrast, baicalein increased the levels of γ-H2AX to a similar extent in both cell types. Transfection with H2AX siRNA further increased baicalein-induced cell death. Additionally, blockade of the AKT pathway by treatment with wortmannin or AKT shRNA lowered the levels of γ-H2AX and enhanced cytotoxicity in baicalein-treated cells. Taken together, our findings suggest that the opposing effects of baicalein on securin and γ-H2AX levels may be involved in the regulation of cell viability and genomic stability by this compound.
authors.affiliation: Molecular Anticancer Laboratory, Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan.
authors.forename: Ren-Huei
authors.initials: RH
authors.lastname: Jiang
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Su
authors.forename: Huei-Fang
authors.initials: HF
authors.lastname: Liu
authors.forename: Hou-Syun
authors.initials: HS
authors.lastname: Huang
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
mesh_terms: D000975:Antioxidants; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation; D042822:Genomic Instability / Q000187:drug effects; D006657:Histones / Q000819:agonists / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D064249:Securin
chemical_list: D000975:Antioxidants; D044950:Flavanones; C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C006680:baicalein; D051057:Proto-Oncogene Proteins c-akt