title: Flavonoids isolated fromCitrus platymammainduced G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells.
abstract: Citrus platymammahort. ex Tanaka belongs to the Rutaceae family and is widely used in folk medicines in Korea due to its anti-proliferative, anti-cancer, anti-oxidant, anti-inflammatory and anti-diabetic activities. However, the molecular mechanism of its anti-cancer effect is not well understood. The present study was conducted to elucidate the anti-cancer effect and molecular mechanism of flavonoids fromCitrus platymamma(FCP) on A549 cells. FCP displayed concentration-dependent inhibition on A549 cells proliferation. Further, flow cytometry revealed that FCP significantly increased the sub-G1 (apoptotic cell population) and G2/M phase population, and the total number of apoptotic cells, in a dose-dependent manner. Nuclear condensation and fragmentation were also observed upon staining with Hoechst 33342 in FCP-treated A549 cells. Immunoblotting demonstrated a dose-dependent downregulation of cyclin B1, cyclin-dependent kinase 1, cell division cycle 25c, pro-caspases -3, -6, -8 and -9, and poly (adenosine diphosphate-ribose) polymerase (PARP) in FCP-treated A549 cells. In addition, FCP induced caspase-3 activation and subsequent PARP cleavage, and increased the B-cell lymphoma (Bcl)-2-associated X protein/Bcl-extra large ratio in A549 cells. These findings suggest that FCP induced G2/M arrest and apoptosis of A549 cells. The present study provides evidence that FCP may be useful in the treatment of human lung cancer.
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-702, Republic of Korea.
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Venu Venkatarame Gowda
authors.initials: VV
authors.lastname: Saralamma
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Gyeong Eun
authors.initials: GE
authors.lastname: Hong
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Silvia
authors.initials: S
authors.lastname: Yumnam
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Raha
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-702, Republic of Korea.
authors.forename: Shobana Nancy
authors.initials: SN
authors.lastname: Charles
authors.affiliation: Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Department of Nursing Science, International University of Korea, Jinju, Gyeongnam 660-759, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Brain Korea 21 Program for Leading Universities and Students, Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Gon Sup
authors.initials: GS
authors.lastname: Kim
keywords: A549 cells; Citrus platymamma; apoptosis; cell cycle; flavonoids; lung cancer