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Identification of novel Bioactivities from Bee venom to target TNF-α for cancer therapy

Cancer is one of the major public health problems globally which arises due to uncontrolled cellular proliferation. Tumor necrosis factor alpha is a member of the TNF/TNFR cytokine superfamily. Currently, the venom from various sources have been widely used in the treatment of cancer. The bioactive present in bee venom has been reported to have potential antimicrobial, anti-inflammatory, and anticancer activity which has drawn the attention to identify the novel inhibitor against TNF-α. Bee venom has been reported to target ovarian, breast, prostate and malignant hepatocellular carcinoma. TNF-α is involved in the maintenance and homeostasis of the immune system, inflammation, and host defense. The oncogenic protein TNF-α plays a critical role in the development of various cancers including renal, lung, liver, prostate, bladder, and breast cancer. TNF-α enhances cancer cell growth, proliferation, invasion, and metastasis, as well as tumor angiogenesis. Due to the high prevalence and mortality, TNF-α associated cancers have remained a significant health problem globally. TNF acts biologically by activating certain signaling pathways such as nuclear factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). Various toxins are being studied as alternatives for cancer treatments, and bee venom and its active components are drawing attention as potential anticancer agents. The present study identifies novel anticancer peptides that target the oncoprotein against life-threatening cancer. Docking calculations indicate that anticancer peptides, namely Melittin, Phospholipase A2, Tertiapin, and Hyaluronidase bind TNF-α respectively with the lowest binding affinity. Interestingly, Mast cell degranulating (MCD) and Apamin have the highest binding affinity with TNF-α in comparison with the above four peptides. The two lead compounds namely MCD and Apamin have the highest docking score -1253.4 and -1067.8 respectively. The present study reveals that the bee venom peptides namely MCD and Apamin interact with TNF-α associated cancer for targeted therapy of cancer. These predicted anticancer peptides are valuable candidates for in vitro or in vivo peptide therapeutic drug studies against the TNF-α associated cancers.

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