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In silico and In vitro Investigation of a Likely Pathway for Anti-Cancerous Effect of Thrombocidin-1 as a Novel Anticancer Peptide

[ Vol. 27 , Issue. 8 ]

Author(s):

Abbas Tanhaian, Elyas Mohammadi, Roghayyeh Vakili-Ghartavol, Mohammad Reza Saberi, Mehdi Mirzayi* and Mahmoud Reza Jaafari*   Pages 751 - 762 ( 12 )

Abstract:


Background: Antimicrobial and antifungal activities of Thrombocidin-1 (TC-1) is shown previously, however, the anti-cancerous feature of this peptide is still uncovered.

Objective: The objective is to evaluate anti-cancerous feature of recombinant TC-1.

Methods: In this study, based on the significant similarity of rTC-1 and IL-8 in case of coding sequence, tertiary structure, and also docking and molecular dynamic simulation (MD) results with CXCR1, a receptor which has positive correlation with different cancers, a likely pathway for anticancerous effect of rTC-1 was proposed. In addition, the coding sequence of TC-1+6xhistidine (rTC-1) was inserted into the pET22b(+) vector and cloned and expressed by E. coli BL21 and finally purified through nickel affinity column. Afterward, the retrieved rTC-1 was used in MTT assay against mouse colon adenocarcinoma, hepatocellular carcinoma, chondrosarcoma, mouse melanoma, and breast adenocarcinoma cell lines to investigate its probable anticancer application.

Results: Docking and MD simulation results showed that rTC-1 and IL-8 share almost the same residues in the interaction with CXCR1 receptor. Besides, the stability of the rTC-1_CXCR11-38 complex was shown during 100ns MD simulation. In addition, the successful expression and purification of rTC-1 depict an 8kD peptide. The IC50 results of MTT assay revealed that rTC-1 has cytotoxic effect on C26-A and SW1353 cancerous cell lines.

Conclusion: Therefore, apart from probable anti-cancerous effect of rTC-1 on C26-A and SW1353 cell lines, this peptide may be able to mimic the anti-cancerous pathway of IL-8.

Keywords:

Thrombocidin-1, recombinant peptide, anti-cancer peptide, cancerous cell lines, molecular dynamic simulations, docking studies.

Affiliation:

School of Medicine, Shahrood University of Medical Science, Shahrood, Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, School of Medicine, Shahrood University of Medical Science, Shahrood, Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad

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