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Improvement of the ...
Improvement of the performance of anticancer peptides using a drug repositioning pipeline
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- Mohammadi, Elyas (författare)
- KTH,Skolan för kemi, bioteknologi och hälsa (CBH),Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran;3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland.
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- Tahmoorespur, Mojtaba (författare)
- Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran
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- Benfeitas, Rui (författare)
- Stockholms universitet,Science for Life Laboratory (SciLifeLab),Institutionen för biokemi och biofysik,National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
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- Altay, Özlem (författare)
- KTH,Skolan för kemi, bioteknologi och hälsa (CBH),Science for Life Laboratory, SciLifeLab
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- Javadmanesh, Ali (författare)
- Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran
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- Lam, Simon (författare)
- Centre for Host–Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, United Kingdom
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- Mardinoglu, Adil (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Centre for Host–Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, United Kingdom
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- Sekhavati, Mohammad Hadi (författare)
- Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran
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(creator_code:org_t)
- 2021-11-14
- 2022
- Engelska.
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 17:1, s. 2100417-
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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-mediated membrane 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, and MCF7) 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 https://github.com/ElyasMo/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.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Cell culture
- Cell membranes
- Chemotherapy
- Drug interactions
- Genes
- Peptides
- Pipelines
- Sulfur compounds
- Cell surfaces
- Chemotherapy treatment
- Chondroitinsulfate
- Drug repositioning
- Drug-resistance
- Heparan sulphate
- LINCS l1000
- Negatively charged
- Performance
- Therapeutic peptides
- Diseases
- antineoplastic agent
- chondroitin 4 sulfate
- chondroitin sulfate
- glycosaminoglycan
- heparan sulfate
- proteoheparan sulfate
- peptide
- A-549 cell line
- antineoplastic activity
- Article
- breast adenocarcinoma
- colorectal adenocarcinoma
- controlled study
- gene expression
- gene expression profiling
- gene interaction
- gene ontology
- gene regulatory network
- Hep-G2 cell line
- HT-29 cell line
- human
- human cell
- liver cell carcinoma
- MCF-7 cell line
- non small cell lung cancer
- transcriptomics
- neoplasm
- Antineoplastic Agents
- Glycosaminoglycans
- Humans
- Neoplasms
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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