کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2569159 | 1128513 | 2012 | 8 صفحه PDF | دانلود رایگان |
2-(3-Methoxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (HKL-1), a 2-phenyl-1,8-naphthyridin-4-one (2-PN) derivative, was synthesized and evaluated as an effective antimitotic agent in our laboratory. However, the molecular mechanisms are uncertain. In this study, HKL-1 was demonstrated to induce multipolar spindles, sustain mitotic arrest and generate multinucleated cells, all of which indicate mitotic catastrophe, in human leukemia HL-60 cells. Western blotting showed that HKL-1 induces mitotic catastrophe in HL-60 cells through regulating mitotic phase-specific kinases (down-regulating CDK1, cyclin B1, CENP-E, and aurora B) and regulating the expression of Bcl-2 family proteins (down-regulating Bcl-2 and up-regulating Bax and Bak), followed by caspase-9/-3 cleavage. These findings suggest that HKL-1 appears to exert its cytotoxicity toward HL-60 cells in culture by inducing mitotic catastrophe.
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► HKL-1 is a potential antimitotic agent against HL-60 cells.
► HKL-1 induces spindle disruption and sustained resulted in mitotic catastrophe.
► CENP-E and aurora B protein expressions significantly reduced.
► Bcl-2 family protein expressions altered and caspase-9/-3 activation.
► HKL-1 is an attractive candidate for possible use as a novel antimitotic agent.
Journal: Toxicology and Applied Pharmacology - Volume 259, Issue 2, 1 March 2012, Pages 219–226