Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2309-2316. doi: 10.31557/APJCP.2022.23.7.2309.
From ancient times to the present-day animal venoms had been used as medicinal and therapeutic agents. Recently it has been reported that the scorpion venom is a potential source of active and therapeutic compounds to design potent drugs against variety of cancerous cells and other diseases. The current study aimed to evaluate the selective toxicity of Iranian Mesobuthus eupeus (IMe) crude venom as a potential source of anticancer compounds on cancerous CLL B-lymphocytes and normal lymphocytes. For this purpose, we isolated cancerous CLL B-lymphocytes and normal lymphocytes from chronic lymphocytic leukemia patients and healthy volunteers. Cancerous CLL B-lymphocytes and normal lymphocytes were treated with different concentration (0, 5, 10, 20, 40 and 80 µg/ml) of IMe crude venom for 12 hours and cytotoxicity, reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and lysosomal membrane integrity were determined. The data demonstrated the significant cytotoxic effect of IMe crude venom on cancerous CLL B-lymphocytes, with a concentration value (IC50) that inhibits 50% of the cell viability of 60 µg/ ml after 12 h of incubation. MTT assay proved that the IMe crude venom is selectively toxic to cancerous CLL B-lymphocytes, and IMe crude venom induced selective cell death via activation of ROS formation and mitochondrial/lysosomal dysfunction. These finding showed that IMe crude venom has a selective mitochondrial/lysosomal-mediated cell death effect on cancerous CLL B-lymphocytes. Therefore, the IMe crude venom and its fractions may be promising in the future anticancer drug development for treatment of CLL and variety of cancers.
从古至今，动物毒液一直被用作药物和治疗剂。最近有报道称，蝎子毒液是一种有潜力的活性和治疗化合物的来源，可以设计出针对多种癌细胞和其他疾病的有效药物。本研究旨在评估伊朗 Mesobuthus eupeus（IME）粗毒液作为潜在抗癌化合物来源对癌细胞 CLL B 淋巴细胞和正常淋巴细胞的选择性毒性。为此，我们从慢性淋巴细胞白血病患者和健康志愿者中分离出癌细胞 CLL B 淋巴细胞和正常淋巴细胞。用不同浓度（0、5、10、20、40 和 80μg/ml）的 IME 粗毒液处理癌细胞 CLL B 淋巴细胞和正常淋巴细胞 12 小时，测定细胞毒性、活性氧（ROS）产生、线粒体膜电位（MMP）崩溃和溶酶体膜完整性。结果表明，IME 粗毒液对癌细胞 CLL B 淋巴细胞具有显著的细胞毒性作用，孵育 12 小时后，抑制 50%细胞活力的浓度值（IC50）为 60μg/ml。MTT 试验证明，IME 粗毒液对癌细胞 CLL B 淋巴细胞具有选择性毒性，IME 粗毒液通过激活 ROS 形成和线粒体/溶酶体功能障碍诱导选择性细胞死亡。这些发现表明，IME 粗毒液对癌细胞 CLL B 淋巴细胞具有选择性的线粒体/溶酶体介导的细胞死亡作用。因此，IME 粗毒液及其馏分有望在未来的抗癌药物开发中用于治疗 CLL 和多种癌症。
