title: Induction of the cell cycle arrest and apoptosis by flavonoids isolated from Korean Citrus aurantium L. in non-small-cell lung cancer cells.
abstract: This study investigated the anti-proliferative and apoptotic effect of flavonoids isolated from Korean Citrus aurantium L. using A549 lung cancer cells. Flavonoids potently inhibited of A549 cells in a dose-dependent manner, whereas flavonoids had a weak inhibitory effect on proliferation of WI-38 cells. Flow cytometry and Western blot analysis showed that flavonoids induced cell cycle arrest at the G2/M checkpoint by controlling the proteins expression level of cyclin B1, cdc2, cdc25c and p21(WAF1/CIP1). Also, flavonoids induced apoptosis through the regulation of the expression of caspases, cleaved PARP and Bax/Bcl-xL ratio. The activity of caspase-3 on A549 cells increased in a dose-dependent manner. These results clearly indicated that the anti-cancer effect of flavonoids on A549 cells follows multiple cellular pathways through G2/M arrest and the induction of apoptosis.
authors.affiliation: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Park
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.forename: Gyeong Eun
authors.initials: GE
authors.lastname: Hong
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Sang Rim
authors.initials: SR
authors.lastname: Kang
authors.forename: Jin A
authors.initials: JA
authors.lastname: Kim
authors.forename: Jue
authors.initials: J
authors.lastname: Zhang
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.forename: Young Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D005419:Flavonoids; D010936:Plant Extracts