Mitotic catastrophe of cancer cells induced by drugs is characterized by low dosage and low toxicity, representing a significant advantage in the cancer treatment. Effective therapeutic options are limited for T-cell malignancies patients who are still treated by high-dose multiagent chemotherapy, potentially followed by hematopoietic stem cell transplantation, highlighting the urgency for identification of more effective anti-T-cell malignancies drugs. The use of antineoplastic drugs which induced tumor cell mitotic catastrophe would be a new strategy for cancer therapy. Nevertheless, there is still no effective mitotic catastrophe agent in T-cell malignancies. Our study showed that nonlethal dosage (ND) of GL-V9 (5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl) butoxy) 4 H-chromen-4-one) (2 µM), a potential anticancer drug, not only attenuated cell growth and survival, but also arrested the cell cycle in G2/M phase and induced multipolar spindles, nuclear alterations (micronucleation and multinucleation), which are the most prominent morphological characteristics of mitotic catastrophe, in T-cell malignancies cell lines including Jurkat, HuT-102, and HuT-78. Moreover, ND GL-V9 could trigger DNA damage, and significantly influence several mitosis-associated proteins. Besides, results showed that ND GL-V9 increased the activity of senescence-associated β-galactosidase (SA-β-Gal) following the induction of mitotic catastrophe in Jurkat and HuT-102 cells with intact p53, while causing apoptosis in p53-deficient HuT-78 cells. We concluded that the anti-T-cell malignancies effects of ND GL-V9 and clarified the precise regulation in the process of mitosis under the action of GL-V9 in T-cell malignancies. Our data provided new evidence for the study of T-cell malignancies treatment associated with mitotic catastrophe and cellular senescence induction.

中文翻译：

---

暴露于非致命剂量的GL-V9的T细胞恶性肿瘤中的有丝分裂灾难和p53依赖性衰老诱导。

由药物诱导的癌细胞的有丝分裂灾难的特征在于低剂量和低毒性，代表了在癌症治疗中的显着优势。对于仍通过大剂量多药化疗，继之以造血干细胞移植治疗的T细胞恶性肿瘤患者，有效的治疗选择受到限制，这突出表明了鉴定更有效的抗T细胞恶性肿瘤药物的紧迫性。使用引起肿瘤细胞有丝分裂灾难的抗肿瘤药物将是癌症治疗的新策略。然而，在T细胞恶性肿瘤中仍然没有有效的有丝分裂突变剂。我们的研究表明，GL-V9（5-羟基-8-甲氧基-2-苯基-7-（4-（吡咯烷-1-基）丁氧基）4 H-色烯-4-酮）的非致死剂量（ND）（ 2 µM），一种潜在的抗癌药物，T细胞恶性肿瘤细胞系不仅减缓细胞生长和存活，而且使G2 / M期细胞周期停滞，并诱导多极纺锤体，核改变（微核化和多核化），这是有丝分裂灾难最突出的形态特征。包括Jurkat，HuT-102和HuT-78。此外，ND GL-V9可能引发DNA损伤，并显着影响几种有丝分裂相关蛋白。此外，结果表明，ND GL-V9在完整的p53的Jurkat和HuT-102细胞中诱导有丝分裂灾难后，增加了衰老相关的β-半乳糖苷酶（SA-β-Gal）的活性，同时导致p53缺陷的细胞凋亡。 HuT-78细胞。我们得出结论，ND GL-V9具有抗T细胞恶性肿瘤的作用，并阐明了GL-V9在T细胞恶性肿瘤作用下有丝分裂过程中的精确调控。我们的数据为与有丝分裂灾难和细胞衰老诱导相关的T细胞恶性肿瘤治疗的研究提供了新的证据。