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AMPK/p53 Axis Is Essential for α-Lipoic Acid-Regulated Metastasis in Human and Mouse Colon Cancer Cells.

Abstract
α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.
AuthorsSunmi Park, Seung Kug Choi, Yura Choi, Hyun-Seuk Moon
JournalJournal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 63 Issue 7 Pg. 882-5 (Oct 2015) ISSN: 1708-8267 [Electronic] England
PMID26312825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Tumor Suppressor Protein p53
  • Thioctic Acid
  • AMP-Activated Protein Kinases
Topics
  • AMP-Activated Protein Kinases (metabolism)
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Colonic Neoplasms (enzymology, pathology)
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Signal Transduction (drug effects)
  • Thioctic Acid (pharmacology)
  • Tumor Suppressor Protein p53 (metabolism)

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