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

Lougin M. Abdel-Ghani; Tarek R. Rahmy; Mohamed M. Tawfik; Ibtisam Kaziri; Ahlam Al-Obaidi; Edward G. Rowan; Robin Plevin; Mohamed A. Abdel-Rahman

doi:10.1016/j.toxicon.2019.06.220

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

Lougin M. Abdel-Ghani, Tarek R. Rahmy, Mohamed M. Tawfik, Ibtisam Kaziri, Ahlam Al-Obaidi, Edward G. Rowan, Robin Plevin, Mohamed A. Abdel-Rahman^*

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

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Abstract

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.

Original language	English
Pages (from-to)	22-31
Number of pages	10
Journal	Toxicon
Volume	168
Early online date	21 Jun 2019
DOIs	https://doi.org/10.1016/j.toxicon.2019.06.220
Publication status	Published - 31 Oct 2019

Funding

Lougin M. Abdel-Ghani acknowledges a Governmental PhD Scholarship (Channel Scheme between Suez Canal University, Egypt and University of Strathclyde, UK) supported by the Egyptian Ministry of Higher Education and Scientific Research to study at the Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. Appendix A

Keywords

apoptosis
cancer therapy
cardiotoxins
cellular uptake
cytotoxic potential
malignant melanoma
ovarian carcinoma
snake venom

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10.1016/j.toxicon.2019.06.220

Abdel-Ghani-etal-Toxicon-2019-snake-venom-of-Naja-nubiae-on-melanoma-and-ovarian-carcinoma-cell-linesAccepted author manuscript, 3.46 MBLicence: CC BY-NC-ND 4.0

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@article{1ee523ba286b4f2dbae77090951bc4d9,

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

abstract = "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.",

keywords = "apoptosis, cancer therapy, cardiotoxins, cellular uptake, cytotoxic potential, malignant melanoma, ovarian carcinoma, snake venom",

author = "Abdel-Ghani, {Lougin M.} and Rahmy, {Tarek R.} and Tawfik, {Mohamed M.} and Ibtisam Kaziri and Ahlam Al-Obaidi and Rowan, {Edward G.} and Robin Plevin and Abdel-Rahman, {Mohamed A.}",

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T1 - Cytotoxicity of Nubein6.8 peptide isolated from the snake venom of Naja nubiae on melanoma and ovarian carcinoma cell lines

AU - Abdel-Ghani, Lougin M.

AU - Rahmy, Tarek R.

AU - Tawfik, Mohamed M.

AU - Kaziri, Ibtisam

AU - Al-Obaidi, Ahlam

AU - Rowan, Edward G.

AU - Plevin, Robin

AU - Abdel-Rahman, Mohamed A.

PY - 2019/10/31

Y1 - 2019/10/31

N2 - 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.

AB - 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.

KW - apoptosis

KW - cancer therapy

KW - cardiotoxins

KW - cellular uptake

KW - cytotoxic potential

KW - malignant melanoma

KW - ovarian carcinoma

KW - snake venom

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DO - 10.1016/j.toxicon.2019.06.220

M3 - Article

AN - SCOPUS:85067877023

SN - 0041-0101

VL - 168

SP - 22

EP - 31

JO - Toxicon

JF - Toxicon

ER -

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

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