Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells

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 mechani...

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Main Authors: Farhana, Aisha, Ee, Avin Hwan Koh, Jia, Bei Tong, Alsrhani, Abdullah, Subbiah, Suresh Kumar, Pooi, Ling Mok
Format: Article
Published: MDPI 2021
Online Access:http://psasir.upm.edu.my/id/eprint/94322/
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author Farhana, Aisha
Ee, Avin Hwan Koh
Jia, Bei Tong
Alsrhani, Abdullah
Subbiah, Suresh Kumar
Pooi, Ling Mok
author_facet Farhana, Aisha
Ee, Avin Hwan Koh
Jia, Bei Tong
Alsrhani, Abdullah
Subbiah, Suresh Kumar
Pooi, Ling Mok
author_sort Farhana, Aisha
building UPM Institutional Repository
collection Online Access
description 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.
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institution Universiti Putra Malaysia
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spelling upm-943222023-05-08T04:00:28Z http://psasir.upm.edu.my/id/eprint/94322/ Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells Farhana, Aisha Ee, Avin Hwan Koh Jia, Bei Tong Alsrhani, Abdullah Subbiah, Suresh Kumar Pooi, Ling Mok 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. MDPI 2021-09-06 Article PeerReviewed Farhana, Aisha and Ee, Avin Hwan Koh and Jia, Bei Tong and Alsrhani, Abdullah and Subbiah, Suresh Kumar and Pooi, Ling Mok (2021) Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells. Molecules, 26 (17). art. no. 5414. pp. 1-13. ISSN 1420-3049 https://www.mdpi.com/1420-3049/26/17/5414 10.3390/molecules26175414
spellingShingle Farhana, Aisha
Ee, Avin Hwan Koh
Jia, Bei Tong
Alsrhani, Abdullah
Subbiah, Suresh Kumar
Pooi, Ling Mok
Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title_full Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title_fullStr Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title_full_unstemmed Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title_short Nanoparticle-encapsulated camptothecin: epigenetic modulation in DNA repair mechanisms in colon cancer cells
title_sort nanoparticle-encapsulated camptothecin: epigenetic modulation in dna repair mechanisms in colon cancer cells
url http://psasir.upm.edu.my/id/eprint/94322/
http://psasir.upm.edu.my/id/eprint/94322/
http://psasir.upm.edu.my/id/eprint/94322/