PPAR Activation and Decreased Proliferation in Oral Carcinoma Cells With 4‐HPR
| Autor: | Raed Abu Ghazallah, Beverly Wuertz, George Harris, Frank G. Ondrey, David Nascene |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Fenretinide Peroxisome Proliferator-Activated Receptors Down-Regulation Peroxisome proliferator-activated receptor Biology Sensitivity and Specificity Sampling Studies 03 medical and health sciences 0302 clinical medicine Internal medicine Tumor Cells Cultured medicine Carcinoma Humans 030223 otorhinolaryngology Receptor Cell Proliferation Probability chemistry.chemical_classification Cell Death Dose-Response Relationship Drug Cell growth Peroxisome medicine.disease Cell counting Endocrinology Otorhinolaryngology Mechanism of action Nuclear receptor chemistry 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research Female Mouth Neoplasms Surgery medicine.symptom |
| Zdroj: | Otolaryngology–Head and Neck Surgery. 133:695-701 |
| ISSN: | 1097-6817 0194-5998 |
| DOI: | 10.1016/j.otohns.2005.07.019 |
| Popis: | To explore whether the mechanism of action of 4-hydroxyphenylretinamide (4-HPR, fenretidine), a synthetic retinoid, involves the functional activation of the nuclear hormone receptor class known as PPARs (peroxisome proliferator-activated receptors). Also, to examine whether anti-proliferative effects of this agent in head and neck cancer cells occur at biologically relevant concentrations.CA 9-22, NA, and UM SCC 11B cells were treated with 4-HPR during their log phase growth and functional activation of PPAR gamma was evaluated by plate luminometry. Cellular proliferation was analyzed by standard MTT cell proliferation assays and cell counting. Student's t tests were performed for all experiments.Significant dose-dependent increases in PPAR gamma activation occurred in response to 4-HPR treatment. Proliferation was significantly inhibited by 4-HPR in a dose-dependent manner as judged by MTT and cell counting assays. These effects occurred at equimolar concentrations in both types of experiments within a range of clinically achievable doses (1-4 microM) of 4-HPR.4-HPR can functionally activate PPAR gamma at clinically achievable doses. Decreased cancer cell proliferation secondary to PPAR gamma activation has been observed in other malignancies as well as upper aerodigestive cancer. PPAR gamma activation by 4-HPR represents another potential anti-cancer mechanism of action for this drug.PPAR gamma activation represents a novel target for anti-cancer therapy for head and neck cancer and the current level of clinical toxicity of 4-HPR would be judged acceptable to utilize this agent alone or in combination chemotherapy. |
| Databáze: | OpenAIRE |
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