PMID- 19838939 OWN - NLM STAT- MEDLINE DCOM- 20100115 LR - 20131121 IS - 1532-7914 (Electronic) IS - 0163-5581 (Linking) VI - 61 IP - 5 DP - 2009 TI - Gamma tocopherol upregulates the expression of 15-S-HETE and induces growth arrest through a PPAR gamma-dependent mechanism in PC-3 human prostate cancer cells. PG - 649-62 LID - 10.1080/01635580902825654 [doi] AB - Chronic inflammation and dietary fat consumption correlates with an increase in prostate cancer. Our previous studies in the colon have demonstrated that gamma-tocopherol treatment could upregulate the expression of peroxisome proliferator-activated preceptors (PPAR) gamma, a nuclear receptor involved in fatty acid metabolism as well modulation of cell proliferation and differentiation. In this study, we explored the possibility that gamma-tocopherol could induce growth arrest in PC-3 prostate cancer cells through the regulation of fatty acid metabolism. Growth arrest (40%) and PPAR gamma mRNA and protein upregulation was achieved with gamma-tocopherol within 6 h. gamma-Tocopherol-mediated growth arrest was demonstrated to be PPAR gamma dependent using the agonist GW9662 and a PPAR gamma dominant negative vector. gamma-tocopherol was shown not to be a direct PPAR gamma ligand, but rather 15-S-HETE (an endogenous PPAR gamma ligand) was upregulated by gamma-tocopherol treatment. 15-Lipoxygenase-2, a tumor suppressor and the enzyme that converts arachidonic acid to 15-S-HETE, was upregulated at 3 h following gamma-tocopherol treatment. Expression of proteins downstream of the PPAR gamma pathway were examined. Cyclin D1, cyclin D3, bcl-2, and NFkappa B proteins were found to be downregulated following gamma-tocopherol treatment. These data demonstrate that the growth arrest mediated by gamma-tocopherol follows a PPAR-gamma-dependent mechanism. FAU - Campbell, Sharon E AU - Campbell SE AD - Department of Biochemistry, East Tennessee State University, Johnson City, TN 37614, USA. campbese@etsu.edu FAU - Musich, Phillip R AU - Musich PR FAU - Whaley, Sarah G AU - Whaley SG FAU - Stimmel, Julie B AU - Stimmel JB FAU - Leesnitzer, Lisa M AU - Leesnitzer LM FAU - Dessus-Babus, Sophie AU - Dessus-Babus S FAU - Duffourc, Michelle AU - Duffourc M FAU - Stone, William AU - Stone W FAU - Newman, Robert A AU - Newman RA FAU - Yang, Peiying AU - Yang P FAU - Krishnan, Koyamangalath AU - Krishnan K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Nutr Cancer JT - Nutrition and cancer JID - 7905040 RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (Ligands) RN - 0 (PPAR gamma) RN - 0 (RNA, Messenger) RN - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid) RN - 8EF1Z1238F (gamma-Tocopherol) RN - EC 1.13.11.33 (ALOX15B protein, human) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - IM MH - Adenocarcinoma/pathology MH - Arachidonate 15-Lipoxygenase/genetics/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Epithelial Cells MH - Gene Expression/*drug effects MH - Gene Knockout Techniques MH - Humans MH - Hydroxyeicosatetraenoic Acids/chemistry/*metabolism MH - Ligands MH - Male MH - PPAR gamma/agonists/genetics/*metabolism MH - Prostate/cytology MH - Prostatic Neoplasms/*pathology MH - Protein Binding MH - RNA, Messenger/metabolism MH - Signal Transduction/drug effects MH - gamma-Tocopherol/metabolism/*pharmacology EDAT- 2009/10/20 06:00 MHDA- 2010/01/16 06:00 CRDT- 2009/10/20 06:00 PHST- 2009/10/20 06:00 [entrez] PHST- 2009/10/20 06:00 [pubmed] PHST- 2010/01/16 06:00 [medline] AID - 914454733 [pii] AID - 10.1080/01635580902825654 [doi] PST - ppublish SO - Nutr Cancer. 2009;61(5):649-62. doi: 10.1080/01635580902825654.