The antipsychotic agent thioridazine (Mellaril) selectively inhibits cancer stem cells without damaging normal blood cells, researchers have discovered. The drug, which targets dopamine receptors to help manage schizophrenia, appears to help the cancer stem cells differentiate into less threatening cell types, thus exhausting the pool of self-renewing cancer cells.
Unlike normal stem cells, cancer stem cells resist differentiating into stable, nondividing cell types. Mickie Bhatia, of McMaster University in Hamilton, Ontario, Canada, and colleagues screened 590 compounds for their activity against human cancer stem cells vs normal human stem cells. The researchers identified 11 compounds that induced differentiation, four of which were deemed candidate compounds. After further testing, only two of them, thioridazine and mefloquine, were found to be worthy of more intense study.
Ultimately, only thioridazine demonstrated a significant impact on inducing differentiation of neoplastic human pluripotent stem cells (hPSCs) vs normal hPSCs, and, unlike chemotherapy and radiation, thioridazine’s actions against cancer cells appear to have no effect on normal stem cells.
As Bhatia’s team explained in the journal Cell, thioridazine was able to destroy leukemia cells, which express a dopamine receptor on their surfaces. (Normal stem cells do not.) The investigators also learned that dopamine receptors appear on some breast cancer stem cells.
These findings suggest that dopamine receptors might serve as a biomarker for tumor-initiating cells, allowing for early detection and treatment of breast cancer and early signs of leukemia progression.