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Iranian Mesobuthus Eupeus Crude Venom Induces Selective Toxicity in Chronic Lymphocytic Leukemia B-Lymphocytes
Ahmad Salimi1,2, Vahed Adhami1,3, Seyyed Hossein Sajjadi Alehashem1,3
1Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Abstract:
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.
Insights
Iranian Mesobuthus eupeus scorpion venom shows selective toxicity against cancerous CLL B-lymphocytes. This venom induces cell death by activating reactive oxygen species and disrupting mitochondrial/lysosomal function, offering potential for new cancer drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Animal venoms have a long history of medicinal use.
- Scorpion venom is increasingly recognized for its therapeutic potential, particularly against cancer.
Purpose of the Study:
- To evaluate the selective toxicity of Iranian Mesobuthus eupeus (IMe) crude venom on cancerous Chronic Lymphocytic Leukemia (CLL) B-lymphocytes and normal lymphocytes.
- To investigate the mechanisms underlying the venom's effects, including reactive oxygen species (ROS) production and mitochondrial/lysosomal dysfunction.
Main Methods:
- Isolation of cancerous CLL B-lymphocytes and normal lymphocytes from patients and healthy volunteers.
- Treatment of lymphocytes with varying concentrations of IMe crude venom (0-80 µg/ml) for 12 hours.
- Assessment of cytotoxicity (MTT assay), ROS production, mitochondrial membrane potential (MMP) collapse, and lysosomal membrane integrity.
Main Results:
- IMe crude venom exhibited significant cytotoxic effects on cancerous CLL B-lymphocytes, with an IC50 of 60 µg/ml after 12 hours.
- The venom demonstrated selective toxicity towards cancerous CLL B-lymphocytes compared to normal lymphocytes.
- IMe crude venom induced selective cell death through ROS activation and mitochondrial/lysosomal dysfunction.
Conclusions:
- IMe crude venom possesses selective mitochondrial/lysosomal-mediated cell death effects on cancerous CLL B-lymphocytes.
- The findings suggest that IMe crude venom and its fractions hold promise for future anticancer drug development, particularly for CLL and other cancers.
