An Analysis on the Viability of DNMT Inhibitors in Cancer Treatment

Aditya Bhaskara; Samarth Shah; Samahith Thellakal

doi:10.58445/rars.839

##article.authors##

Aditya Bhaskara Dougherty Valley High School
Samarth Shah BASIS Independent Fremont Upper
Samahith Thellakal BASIS Independent Fremont Upper

DOI:

https://doi.org/10.58445/rars.839

Keywords:

DNMT, Cancer Treatment, Epigenetics, Decitabine, RG108, Azacitidine, Combination Therapy

Abstract

This paper will explore the viability and options of DNA Methyltransferase inhibitors against cancer. DNA Methyltransferase, DNMT for short, are enzymes that methylate DNA which plays a crucial role in regulating gene expression. Methylation deactivates a gene. DNMTs can cause cancer by many methods such as hypomethylating a tumor suppressor gene, hypomethylated an oncogene or causing some sort of genetic instability. A plausible explanation for it is Epigenetic factors that cause this. This genetic instability can cause an increase in cancer. This can be ceased through the use of DNMT inhibitors such as Decitabine, RG108, and Azacytidine.

References

Turek-Plewa, J., & Jagodziński, P. (2005). THE ROLE OF MAMMALIAN DNA METHYLTRANSFERASES IN THE REGULATION OF GENE EXPRESSION. CELLULAR & MOLECULAR BIOLOGY LETTERS, 10, 631–647. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=b93b4892df137157f81167f67dc6dd70390b8ef0

Łuczak, M., & Jagodzinski, P. (2006). The role of DNA methylation in cancer development. FOLIA HISTOCHEMICA et CYTOBIOLOGICA, 44(3), 143–154. https://journals.viamedica.pl/folia_histochemica_cytobiologica/article/viewFile/4561/3816

Zhang, W., & Xu, J. (2017). DNA methyltransferases and their roles in tumorigenesis. Biomarker Research, 5(1). https://doi.org/10.1186/s40364-017-0081-z

Zhao, S., Zhu, S., Hao, X., Li, P., & Zhang, S. (2011). Effects of DNA methyltransferase 1 inhibition on esophageal squamous cell carcinoma. Diseases of the Esophagus, 24(8), 601–610. https://doi.org/10.1111/j.1442-2050.2011.01199.x

National Cancer Institute. (2021, October 11). What is cancer? National Cancer Institute; National Institutes of Health. https://www.cancer.gov/about-cancer/understanding/what-is-cancer

Chik, F., & Szyf, M. (2010). Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors. Carcinogenesis, 32(2), 224–232. https://doi.org/10.1093/carcin/bgq221

‌Ehrlich, M. (2002). DNA methylation in cancer: too much, but also too little. Oncogene, 21(35), 5400–5413. https://doi.org/10.1038/sj.onc.1205651

Cui, J., Zheng, L., Zhang, Y., & Xue, M. (2021). Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-81971-5

‌

Man, X., Li, Q., Wang, B., Zhang, H., Zhang, S., & Li, Z. (2022). DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy. Frontiers in Cell and Developmental Biology, 10. https://doi.org/10.3389/fcell.2022.916725

Zhang, J., Yang, C., Wu, C., Cui, W., & Wang, L. (2020). DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy. Cancers, 12(8), 2123. https://doi.org/10.3390/cancers12082123

Gnyszka, A., Jastrzebski, Z., & Flis, S. (2013). DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer Research, 33(8), 2989–2996. https://pubmed.ncbi.nlm.nih.gov/23898051/

Togano, T., Nakashima, M., Watanabe, M., Umezawa, K., Watanabe, T., Higashihara, M., & Horie, R. (2013). Synergistic Effect of 5-Azacytidine and NF-κB Inhibitor DHMEQ on Apoptosis Induction in Myeloid Leukemia Cells. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 20(12), 571–577. https://doi.org/10.3727/096504013x13775486749371

Azacitidine - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. Retrieved December 28, 2023, from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/azacitidine#:~:text=Azacitidine%20and%20decitabine%20are%20both ‌

‌Yang, L., Hou, J., Cui, X.-H. ., Suo, L.-N. ., & Lv, Y.-W. . (2017). RG108 induces the apoptosis of endometrial cancer Ishikawa cell lines by inhibiting the expression of DNMT3B and demethylation of HMLH1. European Review for Medical and Pharmacological Sciences, 21(22), 5056–5064. https://doi.org/10.26355/eurrev_201711_13818

PubChem. (n.d.). Azacitidine. Pubchem.ncbi.nlm.nih.gov. Retrieved December 28, 2023, from https://pubchem.ncbi.nlm.nih.gov/compound/Azacitidine#section=Structures

RG108 (N-phthalyl-L-tryptophan): DNMT inhibitor: Medchemexpress. MedchemExpress.com. (n.d.). https://www.medchemexpress.com/RG108.html?utm_source=google&utm_medium=CPC&utm_campaign=US&utm_term=RG108&utm_content=RG108+dnmt+inhibitor

‌

PubChem. (n.d.). Decitabine. Pubchem.ncbi.nlm.nih.gov. Retrieved December 28, 2023, from https://pubchem.ncbi.nlm.nih.gov/compound/451668

Graca, I., Sousa, E., Baptista, T., Almeida, M., Ramalho-Carvalho, J., Palmeira, C., Henrique, R., & Jeronimo, C. (2014). Anti-Tumoral Effect of the Non-Nucleoside DNMT Inhibitor RG108 in Human Prostate Cancer Cells. Current Pharmaceutical Design, 20(11), 1803–1811. https://doi.org/10.2174/13816128113199990516

Paulis, L. E., Mandal, S., Kreutz, M., & Figdor, C. G. (2013). Dendritic cell-based nanovaccines for cancer immunotherapy. Current Opinion in Immunology, 25(3), 389–395. https://doi.org/10.1016/j.coi.2013.03.001

Constantino, J., Gomes, C., Falcão, A., Cruz, M. T., & Neves, B. M. (2016). Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives. Translational Research, 168, 74–95. https://doi.org/10.1016/j.trsl.2015.07.008

‌

Wu, M., Lu, S., Cheng, M., Zhang, H., Jiang, Y.-Z., Lin, S., Yu, L., Zhu, F., Liu, Z., Zhang, Y., Zhang, X., Gao, Q., Chen, D., Li, J., & Yang, L. (2019). Low doses of decitabine improve the chemotherapy efficacy against basal-like bladder cancer by targeting cancer stem cells. Oncogene, 38(27), 5425–5439. https://doi.org/10.1038/s41388-019-0799-1

Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and Biomedical Applications of Exosomes. Science, 367(6478). https://doi.org/10.1126/science.aau6977

‌Hu, C., Liu, X., Zeng, Y., Liu, J., & Wu, F. (2021). DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application. Clinical Epigenetics, 13(1). https://doi.org/10.1186/s13148-021-01154-x

‌ Daskalakis, M., Brocks, D., Sheng, Y.-H., Islam, M. S., Ressnerova, A., Assenov, Y., Milde, T., Oehme, I., Witt, O., Goyal, A., Kühn, A., Hartmann, M., Weichenhan, D., Jung, M., & Plass, C. (2018). Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC-inhibitors. Cell Cycle, 17(7), 811–822. https://doi.org/10.1080/15384101.2018.1442623

‌Kenneth K.W. To, Xing, E., Larue, R. C., & Li, P.-K. (2023). BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications. Molecules, 28(7), 3043–3043. https://doi.org/10.3390/molecules28073043

Kim, H., Jang, H., Cho, H., Choi, J., Hwang, K. Y., Choi, Y., Kim, S. H., & Yang, Y. (2021). Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy. Cancers, 13(17), 4435. https://doi.org/10.3390/cancers13174435

Ou, Y., Zhang, Q., Tang, Y., Lu, Z., Lu, X., Zhou, X., & Liu, C. (2018). DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer. Oncology Reports. https://doi.org/10.3892/or.2018.6210

An Analysis on the Viability of DNMT Inhibitors in Cancer Treatment

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