Chloroquine (CQ) was initially synthesized as an antimalarial agent, but later on, it also shows immunomodulatory, anticancer, and antiviral effects in clinical practice. Although CQ has been used to treat various conditions for more than half century, the underlying mechanisms of its diverse therapeutic actions remain incomplete. In this paper, we hypothesize that targeting three-dimensional genome architecture might be one of the mechanisms of CQ’s diverse therapeutic actions. Based on this hypothesis, new approaches to the treatment and prevention of cancer and coronavirus disease 2019 (COVID-19) are proposed.
Cite this paper
Li, G. (2020). Targeting Three-Dimensional Genome Architecture Might Be One of the Mechanisms of Chloroquine’s Diverse Therapeutic Actions. Open Access Library Journal, 7, e6340. doi: http://dx.doi.org/10.4236/oalib.1106340.
Gao, J., Tian, Z. and Yang, X. (2020) Breakthrough: Chloroquine Phosphate Has Shown Apparent Efficacy in Treatment of COVID-19 Associated Pneumonia in Clinical Studies. BioScience Trends, 14, 72-73.
https://doi.org/10.5582/bst.2020.01047
Gautret. P., Lagier, J.C., Parola, P., Hoang, V.T., Meddeb, L., Mailhe, M. and Doudier, B., et al. (2020) Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial. The International Journal of Antimicrobial Agents, 105949.
https://doi.org/10.1016/j.ijantimicag.2020.105949
Manic, G., Obrist, F., Kroemer, G., Vitale, I. and Galluzzi, L. (2014) Chloroquine and Hydroxychloroquine for Cancer Therapy. Molecular & Cellular Oncology, 1, e29911. https://doi.org/10.4161/mco.29911
Plantone, D. and Koudriavtseva, T. (2018) Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clinical Drug Investigation, 38, 653-671.
https://doi.org/10.1007/s40261-018-0656-y
Duffy. A., Le, J., Sausville, E. and Emadi, A. (2015) Autophagy Modulation: A Target for Cancer Treatment Development. Cancer Chemotherapy and Pharmacology, 75, 439-447. https://doi.org/10.1007/s00280-014-2637-z
Li, G.D. (2006) Nucleus May Be the Key Site of Chloroquine Antimalarial Action and Resistance Development. Medical Hypotheses, 67, 323-326.
https://doi.org/10.1016/j.mehy.2006.02.008
Li, R., Liu, Y., Hou, Y., Gan, J., Wu, P. and Li, C. (2018) 3D Genome and Its Disorganization in Diseases. Cell Biology Toxicology, 34, 351-365.
https://doi.org/10.1007/s10565-018-9430-4
O’Brien, R.L., Allison, J.L. and Hahn, F.E. (1966) Evidence for Intercalation of Chloroquine into DNA. Biochimica et Biophysica Acta, 129, 622-624.
https://doi.org/10.1016/0005-2787(66)90078-5
Li, G.D. (2007) Plasmodium falciparum Chloroquine Resistance Marker Protein (Pfcrmp) May Be a Chloroquine Target Protein in Nucleus. Medical Hypotheses, 68, 332-334. https://doi.org/10.1016/j.mehy.2006.07.016
Misaki, T., Yamaguchi, L., Sun, J., Orii, M., Nishiyama, A. and Nakanishi, M. (2016) The Replication Foci Targeting Sequence (RFTS) of DNMT1 Functions as a Potent Histone H3 Binding Domain Regulated by Autoinhibition. Biochemical and Biophysical Research Communications, 470, 741-747.
https://doi.org/10.1016/j.bbrc.2016.01.029
Matityahu, A. and Onn, I. (2018) A New Twist in the Coil: Functions of the Coiled-Coil Domain of Structural Maintenance of Chromosome (SMC) Proteins. Current Genetics, 64, 109-116. https://doi.org/10.1007/s00294-017-0735-2
Li, G.D. (2016) Certain Amplified Genomic-DNA Fragments (AGFs) May Be Involved in Cell Cycle Progression and Chloroquine Is Found to Induce the Production of Cell-Cycle-Associated AGFs (CAGFs) in Plasmodium falciparum. Open Access Library Journal, 3, e2447. https://doi.org/10.4236/oalib.1102447
Corces, M.R. and Corces, V.G. (2016) The Three-Dimensional Cancer Genome. Current Opinion in Genetics & Development, 36, 1-7.
https://doi.org/10.1016/j.gde.2016.01.002
Ibrahim, D.M. and Mundlos, S. (2020) Three-Dimensional Chromatin in Disease: What Holds Us Together and What Drives Us Apart? Current Opinion in Cell Biology, 64, 1-9. https://doi.org/10.1016/j.ceb.2020.01.003
Yoon, H.Y., Park, H.S., Cho, M.S., Shim, S.S., Kim, Y. and Lee, J.H. (2019) Spontaneous Remission of Advanced Progressive Poorly Differentiated Non-Small Cell Lung Cancer: A Case Report and Review of Literature. BMC Pulmonary Medicine, 19, 210. https://doi.org/10.1186/s12890-019-0978-4
Jessy, T. (2011) Immunity over Inability: The Spontaneous Regression of Cancer. Journal of natural science, biology, and medicine, 2, 43-49.
https://doi.org/10.4103/0976-9668.82318
Dekker, J., Rippe, K., Dekker, M. and Kleckner, N. (2002) Capturing Chromosome Conformation. Science, 295, 1306-1311. https://doi.org/10.1126/science.1067799
Risca, V.I. and Greenleaf, W.J. (2015) Unraveling the 3D Genome: Genomics Tools for Multiscale Exploration. Trends in Genetics, 31, 357-372.
https://doi.org/10.1016/j.tig.2015.03.010