Antitumor Activity of (2E,5Z)-5-(2-Hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one, a Novel Microtubule-Depolymerizing Agent, in U87MG Human Glioblastoma Cells and Corresponding Mouse Xenograft Model

Journal of Pharmacological Sciences

Qiu Zhang²  Hongyu Zhou¹  Bing Yan²  Xiaojun Liu²  Xiue Li²  Changlong Li¹ 

[1] Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital, USA;School of Chemistry and Chemical Engineering, Shandong University, China

关键词: thiazolidinone;    glioblastoma;    microtubule;    microtubule-depolymerizing agent;    U87MG human glioblastoma cell;   

DOI  :  10.1254/jphs.13064FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(4)Supplementary materials(2)Glioblastoma is the most lethal brain cancer. In spite of intensive therapy, the prognosis of patients with glioblastoma is very poor. To discover novel therapeutic agents, we screened a combinatorial compound library containing 372 thiazolidinone compounds using U87MG human glioblastoma cells. (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one (HBPT) was identified as the most potent anti-glioblastoma compound. HBPT inhibits U87MG human glioblastoma cell proliferation with an IC50 of 20 μM, which is almost 5-fold more potent than temozolomide (a widely used drug for treating malignant glioma in the clinic). Mechanistic investigation demonstrated that HBPT is a novel microtubule-depolymerizing agent, which arrests cancer cells at the G2/M phase of the cell cycle and induces cell apoptosis. In the mouse U87MG xenograft model, HBPT elicits a robust tumor inhibitory effect. More importantly, no obvious toxicity was observed for HBPT therapy in animal experiments. These findings indicate that HBPT has the potential to be developed as a novel agent for the treatment of glioblastoma.[Supplementary Tables: available only at http://dx.doi.org/10.1254/jphs.13064FP]

【 授权许可】

Unknown