Cytotoxicity Studies of the Crude venom and Fractions of Persian Gulf Snail (Conus Textile) on Chronic Lymphocytic Leukemia and Normal Lymphocytes

Abstract

Background: Marine animals have been considered by many researchers due to their various pharmacological effects. One group of marine animals that have been studied is cone snails. The conotoxin obtained from these marine animals has various therapeutic effects. Methods: This study was designed to investigate the apoptotic effects of crude venom of Conus textile and its fractions (A and B) on chronic lymphocytic leukemia (CLL) cells. Accordingly, parameters such as cell viability, reactive oxygen species (ROS) level, collapse in mitochondrial membrane potential (MMP), lysosomal membrane damage and caspase-3 activation were evaluated. Results: The results showed that the crude venom (50, 100 and 200 µg/ml) from Conus textile and its fraction B (50, 100 and 200 µg/ml) significantly reduced viability in CLL B-lymphocyte. In addition, exposure of CLL B-lymphocyte to fraction B (50, 100 and 200 µg/ml) was associated with an increase in the level of ROS, the collapse of the MMP, damage to the lysosomal membrane, and activation of caspase-3. Conclusion: According to results, it was concluded that fraction B from crude venom of Conus textile causes selective toxicity on CLL B-lymphocyte with almost no effect on a normal lymphocyte. Furthermore, this venom fraction could be a promising candidate for induction of apoptosis in patients with CLL through the mitochondrial pathway.

Iranian Mesobuthus Eupeus Crude Venom Induces Selective Toxicity in Chronic Lymphocytic Leukemia B-Lymphocytes Through Lysosomal/Mitochondrial Dysfunction and Reactive Oxygen Species Formation

“…In the cancer treatment selective toxicity refers to cytotoxic agents that are more toxic to cancerous cells than human normal cells (Zubrod, 1978). Selective toxicity is the increasing effectiveness of drugs for the treatment of leukemias such chronic lymphocytes leukemia and other cancerous cell lines (Seydi et al, 2016;Salimi et al, 2017;Salimi et al, 2021). Even previous studies have been reported that such selectivity can be achieved even in the patients (Maeda and Khatami, 2018).…”

“…Cancerous B-lymphocytes escape apoptosis by different mechanism which can lead to inhibition of apoptosis (Hassan et al, 2014). Previous studies shown that animal toxins obtained to date mainly from snakes, scorpions, snails and sea cucumbers, have a long history of beneficial use for the induction of cytotoxicity in cancerous cells (Rapôso, 2017;Salimi et al, 2017;Bordon et al, 2020;Salimi et al, 2021). Also, it has been reported that about 60-80% of anti-cancer and antibiotics drugs approved by FDA are derived from natural products (Calixto, 2019).…”

Potential New Therapies “ROS-Based” in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis

“…This conclusion was reached based on the aforementioned findings. In addition, this venom fraction has the potential to be an effective candidate for the induction of apoptosis in individuals who have CLL by means of the mitochondrial route [196].…”

Effects of µ-Conotoxin GIIIB on the cellular activity of mouse skeletal musculoblast: combined transcriptome and proteome analysis

“…Fang et al found that ω-conotoxin (ω-CTX) has a neuroprotective effect on β-amyloid (Aβ)-induced neurotoxicity in Alzheimer’s disease (AD) cell models, increasing cell vitality and inhibiting inflammation and oxidative stress-related factors [ 7 ]. Salimi et al extracted conotoxin directly from cone snails and found that the toxin was selectively toxic to chronic lymphocytic leukemia (CLL) cells and normal lymphocytes, and had a pro-apoptotic effect on CLL cells, but had no significant effect on normal cells [ 8 ]. Oroz-Parra et al analyzed a peptide toxin (S-Cal14.1a) isolated from the sea snail Conus californicus that activates apoptosis in human lung cancer cell lines [ 9 ].…”