دورية أكاديمية
Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target.
| العنوان: | Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target. |
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| المؤلفون: | Wiklund ED; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia., Catts VS, Catts SV, Ng TF, Whitaker NJ, Brown AJ, Lutze-Mann LH |
| المصدر: | International journal of cancer [Int J Cancer] 2010 Jan 01; Vol. 126 (1), pp. 28-40. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1995- : New York, NY : Wiley-Liss Original Publication: 1966-1984 : Genève : International Union Against Cancer |
| مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , Antipsychotic Agents/*pharmacology , Cholesterol/*metabolism , Homeostasis/*drug effects, Base Sequence ; Cell Line, Tumor ; DNA Primers ; Drug Screening Assays, Antitumor ; Humans |
| مستخلص: | The reported reduction in cancer risk in those suffering from schizophrenia may be because antipsychotic medications have antineoplastic effects. In this study, 6 antipsychotic agents with a range of structural and pharmacological properties (reserpine, chlorpromazine, haloperidol, pimozide, risperidone and olanzapine), were screened for their effect on the viability of cell lines derived from lymphoblastoma, neuroblastoma, non-small cell lung cancer and breast adenocarcinoma. We aimed to determine if antipsychotic drugs in general possess cancer-specific cytotoxic potential, and whether it can be attributed to a common mode of action. With the exception of risperidone, all drugs tested displayed selective inhibition of the viability of cancer cell lines compared with normal cells. Using Affymetrix expression microarrays and quantitative real-time polymerase chain reaction, we found that for the antipsychotic drugs, olanzapine and pimozide, cytotoxicity appeared to be mediated via effects on cholesterol homeostasis. The role of cholesterol metabolism in the selective cytotoxicity of these drugs was supported by demonstration of their increased lethality when coadministered with a cholesterol synthesis inhibitor, mevastatin. Also, pimozide and olanzapine showed accelerating cytotoxic effects from 12 to 48 hr in time course studies, mirroring the time-dependent onset of cytotoxicity induced by the amphiphile, U18666A. On the basis of these results, we concluded that the Class II cationic amphiphilic properties of antipsychotic drugs contribute to their cytotoxic effects by acting on cholesterol homeostasis and altering the biophysical properties of cellular membranes, and that drugs affecting membrane-related cholesterol pathways warrant further investigation as potential augmentors of standard cancer chemotherapy. |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Antipsychotic Agents) 0 (DNA Primers) 97C5T2UQ7J (Cholesterol) |
| تواريخ الأحداث: | Date Created: 20090808 Date Completed: 20091130 Latest Revision: 20160303 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/ijc.24813 |
| PMID: | 19662652 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-0215 |
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| DOI: | 10.1002/ijc.24813 |