Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells
| Autor: | Abdullah Alsrhani, Pooi Ling Mok, Aisha Farhana, Suresh Kumar Subbiah, Avin Ee-Hwan Koh, Jia Bei Tong |
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| Rok vydání: | 2021 |
| Předmět: |
animal structures
DNA Repair DNA repair Drug Compounding Pharmaceutical Science Apoptosis Article Epigenesis Genetic Analytical Chemistry Transcriptome QD241-441 transcriptome analysis Nanocapsules Cell Line Tumor Drug Discovery DNA-(Apurinic or Apyrimidinic Site) Lyase Humans Epigenetics HMGB1 Protein Physical and Theoretical Chemistry neoplasms DNA Polymerase III Gene Library Epigenomics Cyclodextrins Base Sequence Chemistry Organic Chemistry Base excision repair Epigenome Antineoplastic Agents Phytogenic digestive system diseases Cell biology DNA-Binding Proteins Drug Liberation Nucleoproteins colon cancer Gene Expression Regulation Chemistry (miscellaneous) Colonic Neoplasms Cancer cell Molecular Medicine nanoparticles Camptothecin Magnetic Iron Oxide Nanoparticles DNA mismatch repair epigenetic modulation |
| Zdroj: | Molecules Volume 26 Issue 17 Molecules, Vol 26, Iss 5414, p 5414 (2021) |
| ISSN: | 1420-3049 |
| Popis: | Molecular crosstalk between the cellular epigenome and genome converge as a synergistic driver of oncogenic transformations. Besides other pathways, epigenetic regulatory circuits exert their effect towards cancer progression through the induction of DNA repair deficiencies. We explored this mechanism using a camptothecin encapsulated in β-cyclodextrin–EDTA–Fe3O4 nanoparticles (CPT-CEF)-treated HT29 cells model. We previously demonstrated that CPT-CEF treatment of HT29 cells effectively induces apoptosis and cell cycle arrest, stalling cancer progression. A comparative transcriptome analysis of CPT-CEF-treated versus untreated HT29 cells indicated that genes controlling mismatch repair, base excision repair, and homologues recombination were downregulated in these cancer cells. Our study demonstrated that treatment with CPT-CEF alleviated this repression. We observed that CPT-CEF exerts its effect by possibly affecting the DNA repair mechanism through epigenetic modulation involving genes of HMGB1, APEX1, and POLE3. Hence, we propose that CPT-CEF could be a DNA repair modulator that harnesses the cell’s epigenomic plasticity to amend DNA repair deficiencies in cancer cells. |
| Databáze: | OpenAIRE |
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