Molecular mechanisms of anti-psychotic drugs for improvement of cancer treatment

Anti-psychotic medications are widely used to treat schizophrenia and bipolar disorder. Besides their medical applications, anti-psychotic drugs have other pharmacological properties which are involved in multiple intracellular functions including metabolism, cell stress, cell-cycle regulation, survival and apoptosis through modulation of cellular signaling pathways such as PI3K/Akt/GSK-3β, STAT3 and wingless (Wnt)-related intracellular signaling. Also, anti-psychotics counteract the growth of tumor cells by stimulating the cellular immune system and natural killer cells. On the other hand, the positive charge and the lipophilicity of anti-psychotics have significant roles in the inhibition of P-gp pumps resulting in accumulation of chemotherapy drugs as well as increasing the cellular susceptibility to chemotherapy, autophagy, angiogenesis inhibition, stem cells differentiation induction and changing the expression of tumor suppressor genes and oncogenes. Overall, anti-psychotics are able to inhibit the proliferation of cancer cells through modulation of different cellular pathways. Anti-psychotics act as anti-cancer drugs and besides can increase the efficacy of anti-cancer agents in cancer cells. In this study, the anti-cancer effects of different anti-psychotic medicines on various malignant tumor cells and their molecular mechanisms have been discussed.