Assessment of cytotoxic properties of tetrahydroisoquinoline oximes in breast, prostate and glioblastoma cancer cells.

Abstract

Tetrahydroisoquinoline (THIQ) oximes have been investigated as antidotes for poisoning by toxic organophosphorus compounds. Recent studies have shown that some THIQ oximes induce cytotoxic effects and trigger apoptosis in various cell types. Since this pathway activation is desirable for anticancer drugs, we further explored the effects of three selected THIQ oximes on well-known cancer cell models: breast (MDA-MB-231 and MCF-7), prostate (PC-3) cancer and malignant glioblastoma (U251). The tested THIQ oximes were cytotoxic to breast cancer cells and, to a lesser extent, to glioblastoma cells, but not to PC-3 cells at concentrations up to 200 µM within a 24-h exposure period. The MCF-7 cells exhibited the highest sensitivity, with all three oximes affecting it in a time-dependent manner (IC₅₀ from 7-74 µM). While the membrane integrity of affected cells was maintained after treatment with the tested THIQ oximes, they disrupted mitochondrial membrane potential and activated caspase 9 indicating triggering of the mitochondria-mediated apoptosis. Overall, these findings suggest that the THIQ oxime scaffold could be a foundation for developing targeted therapies, especially for breast cancer, and other derivatives may be worthier of exploration.