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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. The underlying mechanisms of toxicity of DPDT against tumor cells have previously been poorly explored.
“Together, our results will help to better define DPDT as a potential drug candidate for treating CRC [colorectal cancer].”
The researchers used the colonic HCT116 cancer cells and the MRC5 fibroblasts as models. Their 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, the results of this study 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.”
Keywords: colorectal cancer; HCT116; diphenyl ditelluride; organotellurium; topoisomerase I
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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