Cytotoxicity of Nubein6.8 peptide isolated from the snake venom of Naja nubiae on melanoma and ovarian carcinoma cell lines

• Published in: Toxicon (Oxford) 2019-10, Vol.168, p.22-31
• Main Authors: Abdel-Ghani, Lougin M., Rahmy, Tarek R., Tawfik, Mohamed M., Kaziri, Ibtisam, Al-Obaidi, Ahlam, Rowan, Edward G., Plevin, Robin, Abdel-Rahman, Mohamed A.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer therapy; Cardiotoxins; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; Cellular uptake; Colony-Forming Units Assay; Cytotoxic potential; DNA Damage - drug effects; Elapid Venoms - chemistry; Elapid Venoms - metabolism; Elapid Venoms - toxicity; Humans; Malignant melanoma; Naja; Neoplasms - drug therapy; Ovarian carcinoma; Peptides - chemistry; Peptides - metabolism; Peptides - toxicity; Signal Transduction; Snake venom
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2019.06.220

This study was conducted to examine the cytotoxic effects of Nubein6.8 isolated from the venom of the Egyptian Spitting Cobra Naja nubiae on melanoma (A375) and ovarian carcinoma cell lines and to reveal its mode of action. The size of Nubein6.8 (6801.8 Da) and its N-terminal sequence are similar to cytotoxins purified from the venom of other spitting cobras. Nubein6.8 showed a high significant cytotoxic effect on A375 cell line and moderate effect on A2780. A clonogenic assay showed that Nubein6.8 has a significant long-term potency on A375 cell survival when compared to A2780. The molecular intracellular signaling pathways of Nubein6.8 have been investigated using Western blotting analysis, flow cytometry, and microscale protein labeling. This data revealed that Nubein6.8 has DNA damaging effects and the ability to activate apoptosis in both tumor cell lines. Cellular uptake recordings revealed that the labeled-Nubein6.8 was intracellularly present in A375 cells while A2780 displayed resistance against it. SEM examination showed that Nubein6.8 was found to have high accessibility to malignant melanoma cells. The apoptotic effect of Nubein6.8 was confirmed by TEM examination that revealed many evident characteristics for Nubein6.8 apoptotic efficacy on A375 cell sections. Also, TEM reflected many resistant characteristics that faced Nubein6.8 acquisition through ovarian carcinoma cell sections. Accordingly, the snake venom peptide of Nubein6.8 is a promising template for developing potential cytotoxic agents targeting human melanoma and ovarian carcinoma. •Snake venom peptide Nubein6.8 was isolated from Spitting Cobra N. nubiae.•Nubein6.8 is 6801.8 Da and similar to cytotoxins characterized from other Elapids.•Nubein6.8 revealed potent cytotoxic effect on melanoma cell line (A375).•Nubein6.8 showed moderate cytotoxic effect on ovarian carcinoma cell line (A2780).•Nubein6.8 abled to activate apoptosis in both tumor cell lines.