Evaluation of Cytotoxic and Apoptotic Effects of DT386–BR2: A Promising Anticancer Fusion Protein

Fatemeh Shafiee; Mohammad Rabbani Khorasgani; Ali Jahanian-Najafabadi

doi:10.4103/jrptps.JRPTPS_15_19

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https://doi.org/10.4103/jrptps.JRPTPS_15_19

Evaluation of Cytotoxic and Apoptotic Effects of DT386–BR2: A Promising Anticancer Fusion Protein

Author(s):

Fatemeh Shafiee¹,

Mohammad Rabbani Khorasgani¹,

Ali Jahanian-Najafabadi^1,*

1Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 9, issue 1; 68-72

Published online:Jun 26, 2020

Article type:Research Article

Received:Feb 04, 2019

Accepted:Oct 01, 2019

How to Cite:Fatemeh ShafieeMohammad Rabbani KhorasganiAli Jahanian-NajafabadiEvaluation of Cytotoxic and Apoptotic Effects of DT386–BR2: A Promising Anticancer Fusion Protein.J Rep Pharm Sci.9(1):e147284.https://doi.org/10.4103/jrptps.JRPTPS_15_19.

Abstract

Purpose: In the previous studies, we designed an anticancer immunotoxin containing the catalytic and translocation domains of diphtheria toxin fused to BR2, a buforin II-derived antimicrobial peptide as a cancer-specific cell penetrating peptide, in order to target various cancer cells. The aim of this study was to evaluate the in vitro cytotoxicity of DT386–BR2 against K-562 cells as the most famous cell line for leukemia.
Materials and Methods: MTT and flow-cytometry assays were used for determining the cytotoxic effects and cell death mechanism of DT386–BR2, respectively, against K-562 cell line. The recombinant DT386 and synthetic BR2 were used as the negative control in cytotoxicity assay.
Results: The results of this study showed a significant reduction in survival of K-562 cells caused by DT386– BR2 as compared with BR2 and DT386 fragments. On the contrary, the flow-cytometry results showed apoptosis induction by DT386–BR2 after 12 h in a dose- and time-dependent manner.
Conclusion: DT386–BR2 fusion protein can be used for further preclinical studies for determining its pharmacokinetic/ pharmacodynamic profiles and evaluating its anticancer efficacy in suitable animal models.

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Author(s):

Fatemeh Shafiee:[PubMed][Scholar]
Mohammad Rabbani Khorasgani:[PubMed][Scholar]
Ali Jahanian-Najafabadi:[PubMed][Scholar]