标题：From fighting depression to conquering tumors: a novel tricyclic thiazepine compound as a tubulin polymerization inhibitor
作者：Mu, Y.; Liu, Y.; Xiang, J.; Zhang, Q.; Zhai, S.; Russo, D. P.; Zhu, H.; Bai, X.; Yan, B.
作者机构：[Mu, Y.; Liu, Y.; Zhang, Q.; Zhai, S.; Yan, B.] Shandong Univ, Sch Chem & Chem Engn, 27 Shanda Nanlu, Jinan 250100, Shandong, Peoples R China.; [Xia 更多
通讯作者地址：[Yan, B]Shandong Univ, Sch Chem & Chem Engn, 27 Shanda Nanlu, Jinan 250100, Shandong, Peoples R China.
来源：CELL DEATH & DISEASE
摘要：A novel tricyclic thiazepine derivative, 6-(p-tolyl)benzo[f] pyrido[2,3-b][1,4] thiazepine 11,11-dioxide (TBPT), exhibits potent inhibitory effects in two non-small-cell lung cancer cell lines, H460 and its drug-resistant variant, H460(TaxR), while exhibiting much less toxic effects on normal human fibroblasts. After five injections of TBPT at a dose of 60 mg/kg, it inhibits H460(TaxR) tumor growth in xenografted mouse models by 66.7% without causing observable toxicity to normal tissues. Based on gene perturbation data and a series of investigations, we reveal that TBPT is not a P-glycoprotein substrate and it inhibits microtubule formation by targeting tubulin, thereby causing cell cycle arrest at the G2/M stage and eventually inducing apoptosis. This redeployment of antidepressant compound scaffold for anticancer applications provides a promising future for conquering drug-resistant tumors with fewer side effects.