Potential antitumor mechanisms of phenothiazine drugs

Abstract

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 tumorassociated target proteins play important roles in the process of cell signaling transduction cascades. phenothiazines, antitumor, bioinformatics, target proteins Citation:Qi L, Ding Y Q. Potential antitumor mechanisms of phenothiazine drugs.

Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines

“…Various classes of drugs such as alkylating agents, antimetabolites, antibiotics, hormones and plant alkaloids are used in the traditional cancer chemotherapy 2 . Although selective toxicity is preferable in cancer treatment, the drugs used in clinics have several side effects such as resistance development to the anticancer agents in addition to low selectivities 3 .…”

“…Carbonic anhydrase (CA, EC 4.2.1.1) a zinc-dependent metalloenzyme that catalyzes the reversible hydration of CO 2 . Sixteen different a-CA isoforms have been isolated and characterized so far in mammals: CA I, CA II, CA III, CA VII, CA XIII are cytosolic; CA IV, CA IX, CA XII, CA XIV and CA XV are associated with the cell membrane; CA VA and CA VB are in mitochondria and CA VI is secreted into saliva and milk 4 .…”

DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

“…The CPI profile will be compared against the profiles of our library drugs and potential indications will be suggested based on profile similarities. It has helped different groups of researchers to identify putative targets and potential indications for their molecules28293031. However, the server was developed five years ago and it has two major limitations: (a) the number of predicted indications are limited and biased because of the limited drug library in our server and (b) the indication prediction is based on an unsupervised method, which does not utilize a training process to optimize the prediction for each indication.…”

Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine

“…In this study, the effects of co-treatment using FLU and AZA were analyzed for the first time. Since both drugs showed similar sensitization effects in cancer screening and in the literature (13,28,29), we tested them and compared their effects to those of THIO and MEF. The cancer-sensitizing ability of FLU has been demonstrated in various cancer models (9-12, 28, 29), suggesting that it has potential as a chemotherapeutic agent.…”