PT - JOURNAL ARTICLE AU - Yang C. Wu AU - Mann J. Hour AU - Wing C. Leung AU - Chi Y. Wu AU - Wen Z. Liu AU - Yu H. Chang AU - Hong Z. Lee TI - 2-(Naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone Inhibits Skin Cancer M21 Cell Proliferation through Aberrant Expression of Microtubules and the Cell Cycle AID - 10.1124/jpet.110.176115 DP - 2011 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 942--951 VI - 338 IP - 3 4099 - http://jpet.aspetjournals.org/content/338/3/942.short 4100 - http://jpet.aspetjournals.org/content/338/3/942.full SO - J Pharmacol Exp Ther2011 Sep 01; 338 AB - Microtubules are a proven target for anticancer drug development because they are critical for mitotic spindle formation and the separation of chromosomes at mitosis. 2-(Naphthalene-1-yl)-6-pyrrolidinyl-4-quinazolinone (HL66) induced cell death with the large cells and multiple micronuclei in M21 skin cancer cells. We demonstrated that HL66-induced cell death is caspase-independent and accompanied by the failure of cell cycle progression. Therefore, HL66-induced cell death may be a mitotic catastrophe. HL66 inhibits the dephosphorylation on Thr14 or Tyr15 of cyclin-dependent kinase (Cdk) 1 and the formation of Cdk1/cyclin B1 complex, which might be associated with cell cycle arrest at the S and G2/M phases. HL66 is an antimicrotubule agent by molecular modeling on the basis of ligand binding to tubulin molecule. Furthermore, we also demonstrated that HL66, like vinblastine, is a tubulin-destabilizing agent via microtubule disruption in M21 cells. These results describe a novel pharmacological property of HL66 as a microtubule inhibitor, which may make it an attractive new agent for the treatment of skin cancer.