Gamma (gamma) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (gamma) expression in SW 480 human colon cancer cell lines

• Published in: BMC cancer 2003-10, Vol.3 (1), p.25-25, Article 25
• Main Authors: Campbell, Sharon E, Stone, William L, Whaley, Sarah G, Qui, Min, Krishnan, Koyamangalath
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Humans; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Tocopherols - pharmacology; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Cells, Cultured - drug effects; Up-Regulation - drug effects
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-3-25

Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of gamma-tocopherol is higher than alpha-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used alpha-tocopherol. Recent epidemiological, experimental and molecular studies suggest that gamma-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied alpha-tocopherol. Gamma-tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor gamma (PPARgamma) is a promising molecular target for colon cancer prevention. Upregulation of PPARgamma activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARgamma ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both alpha and gamma tocopherol on the expression of PPARgamma mRNA and protein in SW 480 colon cancer cell lines. We also measured the intracellular concentrations of vitamin E in SW 480 colon cancer cell lines. We have discovered that the alpha and gamma isoforms of vitamin E upregulate PPARgamma mRNA and protein expression in the SW480 colon cancer cell lines. gamma-Tocopherol is a better modulator of PPARgamma expression than alpha-tocopherol at the concentrations tested. Intracellular concentrations increased as the vitamin E concentration added to the media was increased. Further, gamma-tocopherol-treated cells have higher intracellular tocopherol concentrations than those treated with the same concentrations of alpha-tocopherol. Our data suggest that both alpha and gamma tocopherol can upregulate the expression of PPARgamma which is considered an important molecular target for colon cancer chemoprevention. We show that the expression of PPARgamma mRNA and protein are increased and these effects are more pronounced with gamma-tocopherol. Gamma-tocopherol's ability to upregulate PPARgamma expression and achieve higher intracellular concentrations in the colonic tissue may be relevan