PT  - JOURNAL ARTICLE
AU  - YU-HSUN CHANG
AU  - JAI-SING YANG
AU  - SHENG-CHU KUO
AU  - JING-GUNG CHUNG
TI  - Induction of Mitotic Arrest and Apoptosis by a Novel Synthetic Quinolone Analogue, CWC-8, <em>via</em> Intrinsic and Extrinsic Apoptotic Pathways in Human Osteogenic Sarcoma U-2 OS cells
DP  - 2009 Aug 01
TA  - Anticancer Research
PG  - 3139--3148
VI  - 29
IP  - 8
4099  - http://ar.iiarjournals.org/content/29/8/3139.short
4100  - http://ar.iiarjournals.org/content/29/8/3139.full
SO  - Anticancer Res2009 Aug 01; 29
AB  - CWC-8 is a new synthesized novel 2-phenyl-4-quinolone compound in our laboratory which has demonstrated potential antitumor activity. In this study, we have defined the viability inhibition and apoptotic mechanisms of CWC-8 on human osteogenic sarcoma U-2 OS cells. According to the MTT assay, the cell viability was inhibited by CWC-8 in a dose- and time-dependent manner, with an IC50 of 4.97±0.24 μM. CWC-8 treatment induced G2/M arrest and apoptosis in U-2 OS cells by cell cycle and flow cytometry analysis. It also profoundly caused a decrease in polymerized tubulin levels by in vitro tubulin polymerization assay which indicated that the microtubular cytoskeleton appears to be one of the cellular targets in response to CWC-8. Western blotting and CDK1 kinase assay showed that CWC-8 treatment caused a time-dependent increase of Cyclin B and CDK1 protein levels and activity during G2/M arrest. CWC-8 treatment also caused a time-dependent increase in Fas/CD95, FADD, cytosolic cytochrome c, caspase-8/-9/-3 active form, Apaf-1, AIF, Bax protein levels, and decrease in Bcl-2 protein level. CWC-8 also promoted caspase-8/-9 and -3 activities; however, pretreatment of cells with pan-caspase, caspase-8/-9 and -3 inhibitors led to reduced cell growth inhibition action. Taken together, these findings show CWC-8 could be a potential candidate for cancer therapy.