title: Ursolic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis.
abstract: Prostate cancer is one of the most commonly occurring malignancies in men, and because existing treatments are not able to manage this neoplasm adequately, novel approaches are needed. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has strong antitumor activity via the induction of apoptotic cell death in a wide range of tumor cell types and has negligible toxicity to most normal cells, some prostate carcinoma cells are resistant to the apoptotic effects of TRAIL. Therefore, combinatorial approaches with TRAIL and different chemotherapeutic agents have been developed to overcome the resistance of cancer cells to TRAIL. Here, we investigated the sensitizing effects of ursolic acid (UA), a pentacyclic triterpenoid found in many plants, on TRAIL-induced prostate cancer cell apoptosis. We found TRAIL-induced prostate cancer cells apoptosis was significantly enhanced by UA, and that UA induced CHOP-dependent DR5 up-regulation. This study shows the use of UA as a sensitizer for TRAIL-induced apoptotic cell death offers a promising means of enhancing the efficacy of TRAIL-based prostate cancer treatments.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.
authors.forename: Seoung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D051742:Transcription Factor CHOP; D014315:Triterpenes; D000097245:Ursolic Acid