期刊
ARCHIVES OF TOXICOLOGY
卷 94, 期 1, 页码 305-323出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-019-02623-2
关键词
Mitotic catastrophe; Cellular senescence; p53; ND GL-V9; T-cell malignancies
类别
资金
- Drug Innovation Major Project [2017ZX09301014, 2018ZX09711001-003-007, 2017ZX09101003-005-023]
- National Science and Technology Major Project [2018ZX09711001-005-023]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZCX201823]
- Nation Natural Science Foundation of China [81903647, 81503096, 81673461, 81873046, 81830105]
- China Postdoctoral Science Foundation [2018M642373]
- Natural Science Foundation of Jiangsu province [BK20190560, BE2018711]
- Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT-IRT1193]
- Nanjing Medical Science and Technology Development Project [YKK17074]
- Open Project of State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine [E201704]
- Double First-Class University project [CPU2018GF11, CPU2018GF05]
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 mu M), 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 beta-galactosidase (SA-beta-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据