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- Title
Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells.
- Authors
Farhana, Aisha; Koh, Avin Ee-Hwan; Tong, Jia Bei; Alsrhani, Abdullah; Kumar Subbiah, Suresh; Mok, Pooi Ling
- Abstract
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.
- Subjects
DNA repair; CAMPTOTHECIN; COLON cancer; EPIGENETICS; CANCER invasiveness; DNA topoisomerase I; CELL cycle; DNA mismatch repair
- Publication
Molecules, 2021, Vol 26, Issue 17, p5414
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules26175414