Naja Naja Oxiana Venom Fraction Selectively Induces ROS-Mediated Apoptosis in Human Colorectal Tumor Cells by Directly Targeting Mitochondria

Document Type: Research Articles

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Cancer Research Center, Cancer Institute of Iran, Tehran, Iran.

3 Shohadaye Ashayer Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran.

Abstract

 
Objective: To investigate the selective effect of Naja naja oxiana crude venom and its fractions on human colorectal cancer mitochondria to activate apoptosis signaling. Methods: Cells and mitochondria isolated from human cancerous and normal colorectal tissues exposed to N. oxiana crude venom and its fractions obtained from size-exclusion chromatography and then mitochondrial parameters related to up-stream cell death signalling such as reactive oxygen species formation, MMP, mitochondrial swelling, cytochrome c release and ATP content as mitochondrial parameters and activation of caspase3 and finally apoptosis/necrosis % were then assayed as cellular parameters. Result: Our findings indicated that crude venom (15, 30 and 60 μg/ml) and fraction 3; F3; (10, 20 and 40 μg/ml) of N. Oxiana venom induced a significant (p<0.05) increase of reactive oxygen species level, swelling of mitochondria, collapse of mitochondrial membrane potential (MMP), release of cytochrome c, activated caspase3 and decrease ATP content only in colon cancer tissue group but not from the healthy colon tissue group. Our results also showed that fraction 3 of venom decreased the percentage of viable cells and induced apoptosis in cancerous colorectal cells. Conclusion: F3 fraction of N. Oxiana venom is a suitable candidate for further studies as a new drug treatment of colorectal cancer due to its high capacity for induction of apoptosis signaling via mitochondrial pathway.

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