Biotechnology Journal, Volume (17), No (1), Year (2022-1) , Pages (2100417-2100417)

Title : ( Improvement of the performance of anticancer peptides using a drug repositioning pipeline )

Authors: el mo , Mojtaba Tahmoorespur , Rui Benfeitas , Ozlem Altay , Ali Javadmanesh , Simon Lam , Adil Mardinoglu2 , Mohammad Hadi Sekhavati ,

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The use of anticancer peptides (ACPs) as an alternative/complementary strategy to conventional chemotherapy treatments has been shown to decrease drug resistance and/or severe side effects. However, the efficacy of the positively-charged ACP is inhibited by elevated levels of negatively-charged cell-surface components which trap the peptides and prevent their contact with the cell membrane. Consequently, this decreases ACP-mediatedmembrane pore formation and cell lysis. Negatively-charged heparan sulphate (HS) and chondroitin sulphate (CS) have been shown to inhibit the cytotoxic effect of ACPs. In this study, we propose a strategy to promote the broad utilization of ACPs. In this context, we developed a drug repositioning pipeline to analyse transcriptomics data generated for four different cancer cell lines (A549, HEPG2, HT29, andMCF7) treated with hundreds of drugs in the LINCS L1000 project. Based on previous studies identifying genes modulating levels of the glycosaminoglycans (GAGs) HS and CS at the cell surface, our analysis aimed at identifying drugs inhibiting genes correlated with high HS and CS levels. As a result, we identified six chemicals as likely repositionable drugs with the potential to enhance the performance of ACPs. The codes in R and Python programming languages are publicly available in ACPs_HS_HSPGs_CS. As a conclusion, these six drugs are highlighted as excellent targets for synergistic studies with ACPs aimed at lowering the costs associated with ACP-treatment


, cancer, drug repositioning, heparan sulfate, LINCS L1000, therapeutic peptides
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author = {Mo, El and Tahmoorespur, Mojtaba and Rui Benfeitas and Ozlem Altay and Javadmanesh, Ali and Simon Lam and Adil Mardinoglu2 and Sekhavati, Mohammad Hadi},
title = {Improvement of the performance of anticancer peptides using a drug repositioning pipeline},
journal = {Biotechnology Journal},
year = {2022},
volume = {17},
number = {1},
month = {January},
issn = {1860-6768},
pages = {2100417--2100417},
numpages = {0},
keywords = {cancer; drug repositioning; heparan sulfate; LINCS L1000; therapeutic peptides},


%0 Journal Article
%T Improvement of the performance of anticancer peptides using a drug repositioning pipeline
%A Mo, El
%A Tahmoorespur, Mojtaba
%A Rui Benfeitas
%A Ozlem Altay
%A Javadmanesh, Ali
%A Simon Lam
%A Adil Mardinoglu2
%A Sekhavati, Mohammad Hadi
%J Biotechnology Journal
%@ 1860-6768
%D 2022