title: 4-Fluoro-N-butylphenylacetamide (H6) inhibits cell growth via cell-cycle arrest and apoptosis in human cervical cancer cells.
abstract: Phenylacetate induced tumor cytostasis and differentiation. The chemotherapeutic function of the compound in lung cancer has been previously reported, however, whether or not phenylacetate performs other activities is not known. In this study, the potential usage of synthetic phenylacetate derivatives, 4-fluoro-N-butylphenylacetamides (H6) was investigated in human cervical cancer cells. H6 displayed anti-proliferative and apoptosis effects, with an IC(50) of 1.0-1.5 mM and an ID(50) of about 3days. Moreover, it significantly induced apoptosis as evidenced by morphological changes, DAPI and TUNEL staining and DNA fragmentation. H6 increased the expression of Bax protein, whereas it decreased the expression of Bcl-2 protein. H6 also induced accumulation of cytosolic cytochrome c and activation of caspase cascade (caspase-9 and -3), and then DNA fragmentation and apoptosis occurred. The underlying anti-proliferative mechanism for H6 is likely due to the down-regulation of G2/M-phase association cdks and cyclins and up-regulation of p53 to mediate G2/M-phase arrest. Furthermore, the decrease of Bcl-2 and activation of Bax, caspase-9/caspase-3 may be the effectors of H6-induced apoptosis.
authors.affiliation: Department of Obstetrics & Gynecology, College of Medicine, Chung Shan Medical University & Chung Shan Medical University Hospital, Taichung 40242, Taiwan, ROC.
authors.forename: Chung-Hsien
authors.initials: CH
authors.lastname: Liu
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lee
authors.forename: Kan-Jen
authors.initials: KJ
authors.lastname: Tsai
authors.forename: Hsu-Chin
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016195:G2 Phase; D006801:Humans; D020128:Inhibitory Concentration 50; D002583:Uterine Cervical Neoplasms
chemical_list: C470118:4-fluoro-N-butylphenylacetamide; D000081:Acetamides; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins