Nutrition and cancer, 2011-10, Vol.63 (7), p.1133-1142
2011
Details
- Autor(en) / Beteiligte
- Titel
- Pharmacologic Doses of Ascorbic Acid Repress Specificity Protein (Sp) Transcription Factors and Sp-Regulated Genes in Colon Cancer Cells
- Ist Teil von
- Nutrition and cancer, 2011-10, Vol.63 (7), p.1133-1142
- Ort / Verlag
- Philadelphia, PA: Franklin Institute Press
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Ascorbic acid (vitamin C) inhibits cancer cell growth, and there is a controversy regarding the cancer chemoprotective effects of pharmacologic doses of this compound that exhibits prooxidant activity. We hypothesized that the anticancer activity of pharmacologic doses of ascorbic acid (<5 mM) is due, in part, to reactive oxygen species-dependent downregulation of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 and Sp-regulated genes. In this study, ascorbic acid (1-3 mM) decreased RKO and SW480 colon cancer cell proliferation and induced apoptosis and necrosis, and this was accompanied by downregulation of Sp1, Sp3, and Sp4 proteins. In addition, ascorbic acid decreased expression of several Sp-regulated genes that are involved in cancer cell proliferation [hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor and cyclin D1], survival (survivin and bcl-2), and angiogenesis [vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2)]. Other prooxidants such as hydrogen peroxide exhibited similar activities in colon cancer cells, and cotreatment with glutathione inhibited these responses. This study demonstrates for the first time that the anticancer activities of ascorbic acid are due, in part, to ROS-dependent repression of Sp transcription factors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0163-5581, 1532-7914eISSN: 1532-7914DOI: 10.1080/01635581.2011.605984Titel-ID: cdi_fao_agris_US201400145316
- Format
- –
- Schlagworte
- Angiogenesis, anticarcinogenic activity, Anticarcinogenic Agents - pharmacology, Apoptosis, ascorbic acid, Ascorbic Acid - pharmacology, Biological and medical sciences, cell growth, Cell Line, Tumor, cell proliferation, Cell Proliferation - drug effects, Colon - cytology, Colon - drug effects, Colon - pathology, Colonic Neoplasms - metabolism, Colorectal cancer, colorectal neoplasms, Dose-Response Relationship, Drug, Down-Regulation, epidermal growth factor receptors, Feeding. Feeding behavior, Fundamental and applied biological sciences. Psychology, Gastroenterology. Liver. Pancreas. Abdomen, Gene expression, Gene Expression Regulation, Neoplastic, genes, glutathione, hepatocyte growth factor receptor, Humans, hydrogen peroxide, Medical sciences, necrosis, oxygen, Pharmacology, Proteins, Proto-Oncogene Proteins c-met - genetics, Proto-Oncogene Proteins c-met - metabolism, Reactive Oxygen Species - pharmacology, Sp1 Transcription Factor - genetics, Sp1 Transcription Factor - metabolism, Sp3 Transcription Factor - genetics, Sp3 Transcription Factor - metabolism, Sp4 Transcription Factor - genetics, Sp4 Transcription Factor - metabolism, Stomach. Duodenum. Small intestine. Colon. Rectum. Anus, transcription factors, Tumors, Vascular Endothelial Growth Factor Receptor-1 - genetics, Vascular Endothelial Growth Factor Receptor-1 - metabolism, Vascular Endothelial Growth Factor Receptor-2 - genetics, Vascular Endothelial Growth Factor Receptor-2 - metabolism, vascular endothelial growth factors, Vertebrates: anatomy and physiology, studies on body, several organs or systems, Vitamin C