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Article

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

by
Aisha Farhana
1,*,†,
Avin Ee-Hwan Koh
2,†,
Jia Bei Tong
3,
Abdullah Alsrhani
1,
Suresh Kumar Subbiah
3,4,* and
Pooi Ling Mok
1,2
1
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf Province, Saudi Arabia
2
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan 43400, Selangor, Malaysia
3
Department of Medical Microbiology, Universiti Putra Malaysia, Seri Kembangan 43400, Selangor, Malaysia
4
Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Bharath University, Chennai 600073, Tamil Nadu, India
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2021, 26(17), 5414; https://doi.org/10.3390/molecules26175414
Submission received: 30 May 2021 / Revised: 13 July 2021 / Accepted: 14 July 2021 / Published: 6 September 2021
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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.
Keywords: DNA repair; epigenetic modulation; colon cancer; nanoparticles; transcriptome analysis DNA repair; epigenetic modulation; colon cancer; nanoparticles; transcriptome analysis

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MDPI and ACS Style

Farhana, A.; Koh, A.E.-H.; Tong, J.B.; Alsrhani, A.; Kumar Subbiah, S.; Mok, P.L. Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells. Molecules 2021, 26, 5414. https://doi.org/10.3390/molecules26175414

AMA Style

Farhana A, Koh AE-H, Tong JB, Alsrhani A, Kumar Subbiah S, Mok PL. Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells. Molecules. 2021; 26(17):5414. https://doi.org/10.3390/molecules26175414

Chicago/Turabian Style

Farhana, Aisha, Avin Ee-Hwan Koh, Jia Bei Tong, Abdullah Alsrhani, Suresh Kumar Subbiah, and Pooi Ling Mok. 2021. "Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells" Molecules 26, no. 17: 5414. https://doi.org/10.3390/molecules26175414

APA Style

Farhana, A., Koh, A. E.-H., Tong, J. B., Alsrhani, A., Kumar Subbiah, S., & Mok, P. L. (2021). Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells. Molecules, 26(17), 5414. https://doi.org/10.3390/molecules26175414

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