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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hecht, Markus Harrer, Thomas Büttner, Maike Schwegler, Manuela Erber, Sonja Fietkau, Rainer Distel, Luitpold V. |
| Description | Country affiliation: Germany Author Affiliation: Hecht M ( aDepartment of Radiation Oncology bDepartment of Internal Medicine 3 cDepartment of Pathology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.) |
| Abstract | BACKGROUND: Recently, a regression of precancerous lesions in HIV-1-infected patients after initiation of HAART was reported. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) as efavirenz (EFV) might be mediators of this effect, as they are known to have a cytotoxic effect on tumour cells. A potential mechanism involved in this effect may be the activation of the cannabinoid receptor to mediate tumour toxicity. METHODS: Several tumour-derived and fibroblast cell lines were studied. Cytotoxicity of EFV was evaluated by Annexin-Pi staining. The expression of the cannabinoid receptors CB1, CB2 and GPR55 was analysed by western blot, quantitative reverse transcriptase (qRT-PCR) and fluorescence activated cell sorting. The influence of the cannabinoid agonists and antagonists on the effects of EFV was investigated. Furthermore, the effect of EFV on the phosphorylation state of the growth factors Erk, Akt and the tumour suppressor protein p53 was tested. RESULTS: EFV revealed a selective cytotoxic effect on several tumour cell lines, whereas primary fibroblasts were not affected. The cytotoxic effect was associated with the expression of CB1. The combination of EFV with cannabinoid agonists showed an increase in toxicity. The phosphorylation state of Erk and Akt was not affected by EFV, whereas p53 showed an increased phosphorylation. CONCLUSION: EFV has a selective cytotoxic effect on several tumour cells. Furthermore, EFV led to an activating phosphorylation of the tumour suppressor protein p53 going in line with earlier reports that EFV may be antitumourigenic and a potential cytostatic drug. The observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system. |
| File Format | HTM / HTML |
| ISSN | 02699370 |
| Issue Number | 13 |
| Volume Number | 27 |
| e-ISSN | 14735571 |
| Journal | AIDS |
| Language | English |
| Publisher | Lippincott Williams & Wilkins |
| Publisher Date | 2013-08-24 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Immunology Anti-hiv Agents Metabolism Antineoplastic Agents Pharmacology Benzoxazines Receptors, Cannabinoid Blotting, Western Cell Line, Tumor Fibroblasts Drug Effects Flow Cytometry Gene Expression Profiling Humans Real-time Polymerase Chain Reaction Tumor Suppressor Protein P53 Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Immunology and Allergy Immunology |
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