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Brevinin-2R and Derivatives as Potential Anticancer Peptides: Synthesis, Purification, Characterization and Biological Activities

  • Robab Hassanvand Jamadi
  • Hashem YaghoubiEmail author
  • Majid Sadeghizadeh
Article
  • 155 Downloads

Abstract

Brevinin-2R (BR-2R), a novel antimicrobial and anti-cancer peptide and two derivatives, BR-C and BR-D, were well designed, synthesized and purified by RP-HPLC (reverse phase high pressure chromatography). Accuracy was confirmed through mass spectrometry. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay was carried out to determine cytotoxicity of various concentrations of peptides and their anti-proliferative potential. Results indicate that these compounds have significant anticancer activities in vitro on both MCF-7 (human breast adenocarcinoma) and A549 (human lung carcinoma) cancer cells in a concentration-dependent manner, although showed less cytotoxicity on human red blood cells. Further investigation verified that apoptosis induction, confirmed by Annexin V/PI staining and strong sub G1 cell cycle arrest, was observed in treated MCF-7 and A549 cells. Induction of apoptosis and anti-proliferating activity were closely associated with augmentation of caspase-3/7 activity, surging the apoptotic cells with no change in caspase-8 activity. The growth inhibition of BR-2R was exceedingly stronger than two derivatives; on the other hand, MCF-7 was more susceptible to treatment than A549. Findings prominently suggested development of Brevinin-2R and derivatives as novel promising compounds for cancer therapy, which may conquer drug resistance.

Keywords

Anticancer activity Apoptosis Brevinin-2R Cell cycle Chemical synthesis 

Notes

Acknowledgements

This study was financially supported by Islamic Azad University of Ardabil. Authors are grateful to Dr. Hossein Akbari from department of physics at Islamic Azad University, Ardabil Branch and Mehdi Hassanvand Jamadi from Shahid Beheshti University for critically reviewing the manuscript and their invaluable contributions to data analysis.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Robab Hassanvand Jamadi
    • 1
  • Hashem Yaghoubi
    • 2
    Email author
  • Majid Sadeghizadeh
    • 3
  1. 1.Department of Biology, Faculty of ScienceUniversity of Mohaghegh ArdabiliArdabilIran
  2. 2.Department of Biology, Ardabil BranchIslamic Azad UniversityArdabilIran
  3. 3.Department of Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran

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