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- W2897724349 abstract "Abstract Epidemiological observations have shown that schizophrenia patients after long-term drug treatment exhibited reduced tumor incidences. The potential anticancer effects of antipsychotic drugs are subsequently demonstrated. These drugs are of great interest as agents against untreatable brain metastases because of their ability to traverse the blood-brain barrier (BBB). Most drugs tested thus far are the first-generation antipsychotics (FGAs). But their clinical application may be limited due to high risks of deaths in elderly patients. There is an urgent need to find additional BBB-traversing anticancer agents with lower risks of deaths. In this work, we investigated antitumor activities of eight second-generation-antipsychotic (SGA) drugs, since they exhibit lower mortality rates than FGAs. We discovered that sertindole showed broad antiproliferative activities against seven cancer types including 29 cell-lines and exhibited potent effects toward breast cancer cell-lines, with half maximal concentration to inhibit proliferation by 50% (IC 50 ) as low as 800 nM. We further found that sertindole caused cell death through autophagy-associated apoptosis and its directly-binding inhibition of 5-HT6 involved in this process. In xenotransplant mice, sertindole administration approaching maximal therapeutic dose attenuated breast-tumor growth by 22.7%. Therefore, our study reveals promising anticancer potentials of sertindole against breast cancers, with probable applications for breast-to-brain metastases." @default.
- W2897724349 created "2018-10-26" @default.
- W2897724349 creator A5007405399 @default.
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- W2897724349 date "2018-10-25" @default.
- W2897724349 modified "2023-10-03" @default.
- W2897724349 title "Antiproliferative activities of the second-generation antipsychotic drug sertindole against breast cancers with a potential application for treatment of breast-to-brain metastases" @default.
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- W2897724349 doi "https://doi.org/10.1038/s41598-018-33740-0" @default.
- W2897724349 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6202417" @default.
- W2897724349 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30361678" @default.
- W2897724349 hasPublicationYear "2018" @default.
- W2897724349 type Work @default.