title: 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.
abstract: 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].
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Xiue
authors.initials: X
authors.lastname: Li
authors.forename: Changlong
authors.initials: C
authors.lastname: Li
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology*; D009368:Neoplasm Transplantation; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D000077204:Temozolomide; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
chemical_list: C587443:5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino)thiazolidin-4-one; D000970:Antineoplastic Agents; D010647:Phenyl Ethers; D053778:Thiazolidines; D050257:Tubulin Modulators; D003606:Dacarbazine; D000077204:Temozolomide