دورية أكاديمية
Novel oligomeric proanthocyanidin derivatives interact with membrane androgen sites and induce regression of hormone-independent prostate cancer
| العنوان: | Novel oligomeric proanthocyanidin derivatives interact with membrane androgen sites and induce regression of hormone-independent prostate cancer |
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| المؤلفون: | Kampa, M., Theodoropoulou, K., Mavromati, F., Pelekanou, V., Notas, G., Lagoudaki, E. D., Nifli, A. P., Morel-Salmi, C., Stathopoulos, E. N., Vercauteren, J., Castanas, E. |
| المصدر: | http://www.scopus.com/inward/record.url?eid=2-s2.0-79953013333&partnerID=40&md5=e1567c040c59f2be37b8b1da02f426afTest. |
| سنة النشر: | 2011 |
| المجموعة: | University of Thessaly Institutional Repository / Ιδρυματικό Αποθετήριο Πανεπιστημίου Θεσσαλίας |
| مصطلحات موضوعية: | alanine aminotransferase, albumin conjugate, androgen receptor, aspartate aminotransferase, bovine serum albumin, epicatechin, epicatechin gallate, flavanol derivative, grape seed extract, proanthocyanidin derivative, procyanidin b1, procyanidin b2, procyanidin b3, procyanidin B4, testosterone derivative, unclassified drug, alanine aminotransferase blood level, animal experiment, animal model, animal tissue, antineoplastic activity, article, aspartate aminotransferase blood level, cancer cell culture, cancer regression, cell proliferation, cell strain LNCaP, controlled study, drug structure, grape |
| الوصف: | Prostate cancer is the most common malignancy among men in Western societies, and current therapeutic approaches are evolving to manage growth, recurrence, and mortality neoplasia. Membrane androgen receptors (mARs) have been characterized in human prostate cancer, being preferentially expressed in tumor rather than benign gland areas. Furthermore, mAR agonists (protein-conjugated testosterone) decrease in vitro prostate cancer cell growth and induce apoptosis, whereas in vivo they regress growth of tumor xenografts alone or in combination with taxane drugs. In this respect, targeting mARs might be a novel therapeutic approach in prostate cancer. In our search for new small-molecule ligands of mAR, we report that flavanol dimers B1-B4 (oligomeric procyanidins) decrease in vitro growth of the androgen-sensitive (LnCaP) and androgen-resistant (DU145) human prostate cancer cell lines in the following order: B3 = B4 > B2 ≫ B1 (LnCaP) and B2 ≫ B3 = B4 ≫ B1 (DU145). Some of these analogs were previously shown to trigger signaling cascades similar to testosterone-bovine serum albumin (BSA) conjugate. Galloylation does not confer an additional advantage; however, oleylation increases the dimers' antiproliferative potency by a factor of 100. In addition, we report that B2, oleylated or not, displaces testosterone from mARs with an IC 50 value at the nanomolar range and induces DU145 tumor xenograft regression by 50% (testosterone-BSA 40%). In this respect, oleylated B2 is a potent small-molecule agonist of mAR and could be a novel therapeutic agent for advanced prostate cancer, especially when taking into account the absence of androgenic actions and (liver) toxicity. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | 223565; http://hdl.handle.net/11615/28816Test |
| DOI: | 10.1124/jpet.110.177246 |
| الإتاحة: | https://doi.org/10.1124/jpet.110.177246Test http://hdl.handle.net/11615/28816Test |
| رقم الانضمام: | edsbas.C007C014 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1124/jpet.110.177246 |
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