title: Casticin induced apoptotic cell death and altered associated gene expression in human colon cancer colo 205 cells.
abstract: Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca2+productions, level of mitochondria membrane potential (ΔΨm) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death. Casticin induced cell morphological changes, decreased cell viability and induced G2/M phase arrest in colo 205 cells. Casticin increased ROS production but decreased the levels of ΔΨm, and Ca2+, increased caspase-3, -8, and -9 activities. The cDNA microarray indicated that some of the cell cycle associated genes were down-regulated such as cyclin-dependent kinase inhibitor 1A (CDKN1A) (p21, Cip1) and p21 protein (Cdc42/Rac)-activated kinase 3 (PAK3). TNF receptor-associated protein 1 (TRAP1), CREB1 (cAMP responsive element binding protein 1) and cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27, Kip1) genes were increased but matrix metallopeptidase 2 (MMP-2), toll-like receptor 4 (TLR4), PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, bet), and CaMK4 (calcium/calmodulin-dependent protein kinase IV) genes were inhibited. Results suggest that casticin induced cell apoptosis via the activation of the caspase- and/or mitochondria-dependent signaling cascade, the accumulation of ROS and altered associated gene expressions in colo 205 human colon cancer cells.
authors.affiliation: Graduate Institute of Clinical of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hung-Sheng
authors.initials: HS
authors.lastname: Shang
authors.affiliation: Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei, Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei, Taiwan.|Department of Restaurant, Hotel and Institutional Management, Fu-Jen Catholic University, New Taipei city, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: Graduate Institute of Basic Medicine, Fu-Jen Catholic University, New Taipei city, Taiwan.
authors.forename: Han-Sun
authors.initials: HS
authors.lastname: Chiang
authors.affiliation: Department of Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Hain
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Nephrology, Department of Medicine, Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D050760:Cyclin-Dependent Kinase Inhibitor p27; C054133:casticin; D020169:Caspases; D002118:Calcium
keywords: Casticin; apoptosis; cDNA microarray; colo 205 cells; mitochondria