Leptin acts as a mitogenic and antiapoptotic factor for colonic cancer cells

• Published in: British journal of surgery Vol. 94; no. 3; pp. 346 - 354
• Main Authors: Hoda, M. R., Keely, S. J., Bertelsen, L. S., Junger, W. G., Dharmasena, D., Barrett, K. E.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2007; Wiley
• Subjects: Analysis of Variance; Apoptosis; Biological and medical sciences; Cell Proliferation; Colonic Neoplasms - etiology; Enzyme-Linked Immunosorbent Assay; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Humans; Immunoblotting; Leptin - metabolism; Medical sciences; Mitogen-Activated Protein Kinases - physiology; Obesity - complications; Phosphatidylinositol 3-Kinases - physiology; Risk Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumors; Cell factor; Legislation; Adipokine; Malignant tumor; Colonic disease; Medicine; Antiapoptotic agent; Colon cancer; Treatment; Surgery; Leptin; Digestive diseases; Intestinal disease; Tumor cell; Apoptosis
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1002/bjs.5530

Background: Obesity is associated with increased levels of leptin. The mitogenic actions of leptin have been identified in various cell types. Because obesity may be a risk factor for colonic cancer, the proliferative and antiapoptotic effects of leptin on colonic cancer cells and the role of mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3‐K) signalling were investigated. Methods: Three human colonic cancer cell lines (T84, HT29/Cl.19A and Caco‐2) were treated with leptin. Cell proliferation was measured using the XTT® colorimetric assay and apoptosis by a cell death enzyme‐linked immunosorbent assay. Inhibitors of MAPK and PI3‐K were used to evaluate the role of these signalling pathways. Phosphorylation of the downstream components extracellular signal‐regulated kinase (ERK) 1/2 and Akt was detected by western blotting. Results: Leptin increased cell number in all cell lines in a dose‐dependent manner and reduced the number of apoptotic cells in a cell line‐dependent manner. Leptin also caused ERK1/2 and Akt phosphorylation. Pretreatment with inhibitors of MAPK and PI3‐K inhibited these responses, attenuated the mitogenic action of leptin and abolished its antiapoptotic effects. Conclusion: Chronic increases in leptin concentration may enhance the growth of colonic cancers via MAPK and PI3‐K pathways. These effects of leptin could provide a link between obesity and colonic cancer, and may represent a target for anticancer drug development. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Could be a link between obesity and colonic cancer