Potential antitumor mechanisms of phenothiazine drugs

Lu Qi, YanQing Ding

In this study, three kinds of phenothiazine drugs were analyzed to explore their potential antitumor mechanisms. First, target proteins that could interact with chlorpromazine, fluphenazine and trifluoperazine were predicted. Then, the target proteins of the three drugs were intersected. Cell signaling pathway enrichment and related disease enrichment were conducted for the intersected proteins to extract the enrichment categories associated with tumors. By regulation network analysis of the protein interactions, the mechanisms of action of these target proteins in tumor tissue were clarified, thus confirming the potential antitumor mechanisms of the phenothiazine drugs. The final results of cell signaling pathway enrichment and related disease enrichment showed that the categories with the highest score were all found in tumors. Target proteins belonging to the tumor category included signaling pathway members such as Wnt, MAPK and retinoic acid receptor. Moreover, another target protein, MAPK8, could indirectly act on target proteins CDK2, IGF1R, GSK3B, RARA, FGFR2 and MAPK10, thereby affecting tumor cell division and proliferation. Therefore, phenothiazine drugs may have potential antitumor effects, and tumor-associated target proteins play important roles in the process of cell signaling transduction cascades.