title: Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.
abstract: Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.
authors.affiliation: Department of Radiation Oncology, Chi Mei Hospital, Liouying, Tainan, Taiwan.
authors.forename: Henry W C
authors.initials: HW
authors.lastname: Leung
authors.forename: W H
authors.initials: WH
authors.lastname: Yang
authors.forename: M Y
authors.initials: MY
authors.lastname: Lai
authors.forename: C J
authors.initials: CJ
authors.lastname: Lin
authors.forename: H Z
authors.initials: HZ
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D017931:DNA Primers; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008517:Phytotherapy; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031364:Scutellaria baicalensis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D012313:RNA