DPDT: Anticancer Activity and DNA Topoisomerase I Poisoning in Colon Cancer Cells | Oncotarget
Channel: Oncotarget
Date: 2023-06-23

Oncotarget published this research paper on June 21, 2023 in Volume 14, entitled, “Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells" by researchers from Department of Biophysics/Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris F-75012, France; Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre – UFCSPA, Porto Alegre - RS, Brazil; Department of Postgraduate Program in Molecular and Cell Biology Applied to Health, Lutheran University of Brazil (ULBRA), Canoas, Brazil; Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria; Postgraduate Program in Biotechnology and Medical Sciences, University of Vale do Taquari - UNIVATES, Lajeado - RS, Brazil.
#cancer  #colorectalcancer  #coloncancer  #drugdiscovery  #cancerresearch  #research  #researchpaper  #openaccess  #openscience   #peerreview   #journal   #publication  #publishing  #meded

DOI - https://doi.org/10.18632/oncotarget.28465

Correspondence to - João Antonio Pêgas Henriques - pegas.henriques@ufrgs.br, and Alexandre Escargueil - alexandre.escargueil@gmail.com

Abstract

Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. Considering that the underlying mechanisms of toxicity of DPDT against tumor cells have been poorly explored, the objective of our study was to investigate the effects of DPDT against both human cancer and non-tumorigenic cells. As a model, we used the colonic HCT116 cancer cells and the MRC5 fibroblasts. Our results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells. Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, our results show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning. This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.

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Keywords - colorectal cancer, HCT116, diphenyl ditelluride, organotellurium, topoisomerase I

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