Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-09, Vol.26 (17), p.5414
• Main Authors: Farhana, Aisha, Koh, Avin Ee-Hwan, Tong, Jia Bei, Alsrhani, Abdullah, Kumar Subbiah, Suresh, Mok, Pooi Ling
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Base excision repair; Base Sequence; Camptothecin; Camptothecin - chemistry; Camptothecin - pharmacology; Cancer therapies; Cell cycle; Cell Line, Tumor; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colorectal cancer; Crosstalk; Cyclodextrins; Cyclodextrins - chemistry; Deoxyribonucleic acid; DNA; DNA methylation; DNA Polymerase III - genetics; DNA Polymerase III - metabolism; DNA repair; DNA Repair - drug effects; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Compounding; Drug Liberation; Encapsulation; Epigenesis, Genetic - drug effects; epigenetic modulation; Epigenetics; Ethylenediaminetetraacetic acids; Gene Expression Regulation; Gene Library; Genes; Genomes; Harnesses; HMGB1 protein; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Homology; Humans; Iron oxides; Magnetic Iron Oxide Nanoparticles - chemistry; Mismatch repair; Nanocapsules - chemistry; Nanoparticles; Nucleoproteins - genetics; Nucleoproteins - metabolism; Recombination; Repair; transcriptome analysis; Transcriptomes; β-Cyclodextrin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26175414

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-Fe O 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 , , and . 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.