School of Chinese Medicine
Effects of adrenaline in human colon adenocarcinoma HT-29 cells
Aims: Stress has been implicated in the development of cancers. Adrenaline levels are increased in response to stress. The effects of adrenaline on colon cancer are largely unknown. The aims of the study are to determine the effects of adrenaline in human colon adenocarcinoma HT-29 cells and the possible underlying mechanisms involved. Main methods: The effect of adrenaline on HT-29 cell proliferation was determined by [3H] thymidine incorporation assay. Expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were detected by Western blot. Matrix metalloproteinase-9 (MMP-9) activity and prostaglandin E2 (PGE2) release were determined by zymography and enzyme immunoassay, respectively. Key findings: Adrenaline stimulated HT-29 cell proliferation. This was accompanied by the enhanced expression of COX-2 and VEGF in HT-29 cells. Adrenaline also upregulated MMP-9 activity and PGE2 release. Adrenaline stimulated HT-29 cell proliferation which was reversed by COX-2 inhibitor sc-236. COX-2 inhibitor also reverted the action of adrenaline on VEGF expression and MMP-9 activity. Further study was performed to determine the involvement of β-adrenoceptors. The stimulatory action of adrenaline on colon cancer growth was blocked by atenolol and ICI 118,551, a β1- and β2-selective antagonist, respectively. This signified the role of β-adrenoceptors in this process. In addition, both antagonists also abrogated the stimulating actions of adrenaline on COX-2, VEGF expression, MMP-9 activity and PGE2 release in HT-29 cells. Significance: These results suggest that adrenaline stimulates cell proliferation of HT-29 cells via both β1- and β2-adrenoceptors by a COX-2 dependent pathway. © 2011 Elsevier Inc. All rights reserved.
Adrenaline, Colon cancer, COX-2, Stress
Source Publication Title
Wong, Helen P. S., Judy W. C. Ho, Marcel W. L. Koo, Le Yu, William K. K. Wu, Emily K. Y. Lam, Emily K. K. Tai, Joshua K. S. Ko, Vivian Y. Shin, Kent Man Chu, and Chi Hin Cho. "Effects of adrenaline in human colon adenocarcinoma HT-29 cells." Life Sciences 88.25-26 (2011): 1108-1112.