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

Abstract

<br /> <strong><span style="font-size: small;">Objective: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">To investigate the selective effect of </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Naja naja oxiana </span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">crude venom and its fractions on human colorectal cancer mitochondria to activate apoptosis signaling. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Cells and mitochondria isolated from human cancerous and normal colorectal tissues exposed to </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">N. oxiana </span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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 </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">and activation of caspase3 and finally apoptosis/necrosis % were then assayed as cellular parameters. </span></span><strong><span style="font-size: small;">Result: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">findings indicated that crude venom (15, 30 and 60 μg/ml) and fraction 3; F3; (10, 20 and 40 μg/ml) of </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">N. Oxiana </span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">venom induced a significant (p<0.05) increase of reactive oxygen species level, swelling of mitochondria, collapse </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">F3 fraction of </span></span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">N. Oxiana </span></span></em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">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. </span></span>