Background:
Cancer is a major cause of death worldwide, despite many different drugs
available to treat the disease. This high mortality rate is largely due to the complexity of the disease,
which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching
for novel drugs that can target different and multiple aspects of cancer.
Experimental:
After a screening, we selected one novel molecule, out of ninety-four triazole derivatives,
that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7,
with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease
in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria
metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the
cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed
when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor
implants, the drug preventing tumor growth presented no toxicity for the animal and without altering
biochemical markers of hepatic function.
Results and Conclusion:
The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial
metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a
promising drug for controlling breast cancer with minimal undesirable effects.
Targeting dePARylation selectively suppresses DNA repair–defective and PARP inhibitor–resistant malignancies
