Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Expression and Characterization of a Novel Recombinant Cytotoxin II from Naja naja oxiana Venom: A Potential Treatment for Breast Cancer

Afshin Derakhshani
ORCID logo ,
Nicola Silvestris
ORCID logo ,
Khalil Haji‐Asgarzadeh
ORCID logo ,
Sara Mahmoudzadeh
,
Mohammad Fereidouni
,
Angelo Virgilio Paradiso
ORCID logo ,
Oronzo Brunetti
ORCID logo ,
Deyhim Atarod
,
Hossein Safarpour
* ORCID logo ,
Behzad Baradaran
*
Version 1 : Received: 5 May 2020 / Approved: 6 May 2020 / Online: 6 May 2020 (15:12:05 CEST)

A peer-reviewed article of this Preprint also exists.

Derakhshani, A.; Silvestris, N.; Hajiasgharzadeh, K.; Mahmoudzadeh, S.; Fereidouni, M.; Paradiso, A.V.; Brunetti, O.; Atarod, D.; Safarpour, H.; Baradaran, B. Expression and Characterization of a Novel Recombinant Cytotoxin II from Naja Naja Oxiana Venom: A Potential Treatment for Breast Cancer. International Journal of Biological Macromolecules 2020, 162, 1283–1292, doi:10.1016/j.ijbiomac.2020.06.130. Derakhshani, A.; Silvestris, N.; Hajiasgharzadeh, K.; Mahmoudzadeh, S.; Fereidouni, M.; Paradiso, A.V.; Brunetti, O.; Atarod, D.; Safarpour, H.; Baradaran, B. Expression and Characterization of a Novel Recombinant Cytotoxin II from Naja Naja Oxiana Venom: A Potential Treatment for Breast Cancer. International Journal of Biological Macromolecules 2020, 162, 1283–1292, doi:10.1016/j.ijbiomac.2020.06.130.

Abstract

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 µg mL-1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs.

Keywords

breast cancer; snake venom; cytotoxin II; recombinant protein; apoptosis; cell cycle progression; cytotoxicity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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