中华眼镜蛇毒液中的细胞毒素1可诱导白血病细胞发生坏死性凋亡。
Cytotoxin 1 from Naja atra Cantor venom induced necroptosis of leukemia cells.
作者信息
Liu Yamin, Ming Wei, Wang Yan, Liu Sihong, Qiu Yanfen, Xiang Yongxin, Hu Lili, Fan Lingjie, Peng Xiang, Wang Han, Kong Tianhan, Dong Weihua, Guo Qifeng
机构信息
Department of Orthopaedics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, China.
Medical Humanities Teaching and Research Office, Hetao College, Bayannur City, Inner Mongolia Autonomous Region, 015000, China.
出版信息
Toxicon. 2019 Jul;165:110-115. doi: 10.1016/j.toxicon.2019.04.012. Epub 2019 Apr 25.
BACKGROUND
Cytotoxin 1 (CTX1) purified from Naja atra Cantor venom could inhibit cancer cell proliferation, but the mechanism is not clear. This study aimed to investigate the mechanism by which leukemia cells are killed by CTX1.
MATERIALS AND METHODS
HL-60 and KG1a cells were treated with CTX1 and the cell death was detected.
RESULTS
The viability of HL-60 and KG1a cells decreased in a dose- and time-dependent manner after treatment with CTX1. CTX1 mainly induced late apoptosis and necrosis. The cell death induced by CTX1 could be rescued by specific necroptosis inhibitor Nec-1 but not by caspase inhibitor Z-VAD-fmk in HL-60 cells. In addition, CTX1 increased lysosome membrane permeability (LMP) and release of cathepsin B.
CONCLUSION
CTX1 could induce necroptosis in leukemia cells, and it is related to LMP increase and cathepsin release. CTX1 could be a promising anti-cancer drug for leukemia therapy.
背景
从眼镜蛇毒液中纯化得到的细胞毒素1（CTX1）可抑制癌细胞增殖，但其机制尚不清楚。本研究旨在探讨CTX1杀死白血病细胞的机制。
材料与方法
用CTX1处理HL-60和KG1a细胞，并检测细胞死亡情况。
结果
用CTX1处理后，HL-60和KG1a细胞的活力呈剂量和时间依赖性下降。CTX1主要诱导晚期凋亡和坏死。在HL-60细胞中，CTX1诱导的细胞死亡可被特异性坏死性凋亡抑制剂Nec-1挽救，但不能被半胱天冬酶抑制剂Z-VAD-fmk挽救。此外，CTX1增加了溶酶体膜通透性（LMP）和组织蛋白酶B的释放。
结论
CTX1可诱导白血病细胞发生坏死性凋亡，且与LMP增加和组织蛋白酶释放有关。CTX1可能是一种有前途的用于白血病治疗的抗癌药物。
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