Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review

Phenothiazine derivatives have been used for decades as antipsychotic drugs in multiple mental health and physical conditions treatment (schizophrenia, mania in bipolar disorder, and psychosis). Epidemiological studies have shown that people with schizophrenia are less likely to suffer from cancer, which indicates the ability of antipsychotics to inhibit the development of cancer cells. It is our third review about the impact of phenothiazine derivatives on cell death. Here, we focused on apoptosis. We selected 92 papers that investigated the effect of phenothiazine derivatives on the apoptosis process in normal and cancer cell lines. Chlorpromazine, fluphenazine, levomepromazine, mepazine, perphenazine, promazine, promethazine, thioridazine, trifluoperazine, and trifluoperazine analog (3dc) more often induce apoptosis in cancer cell lines, human hepatocytes, and lymphocytes, and the final effect depends on the type and concentration of drug used, the type of cell line, and the methodology used. The obtained results allow for a better understanding of the biological action of phenothiazine derivatives and will help reposition this group of drugs to cancer treatment, resulting in faster, safer, easier, and cheaper therapy.