Open Access

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets

  • Authors: Srinivasan Marimuthu, Raghavender S.V. Chivukula, Lloyd F. Alfonso, Majid Moridani, Fred K. Hagen, G. Jayarama Bhat
  • View Affiliations

  • Published online on: Monday, July 4, 2011
  • Pages: 1273-1283
  • DOI: 10.3892/ijo.2011.1113

Abstract

Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno­blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.
Journal Cover

November 2011
Volume 39 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Marimuthu, S., Chivukula, R., Alfonso, L., Moridani, M., Hagen, F., & Bhat, G. (2011). Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets. International Journal of Oncology, 39(5), 1273-1283.
MLA
Marimuthu, Chivukula, Alfonso, Moridani, Hagen, and G. Bhat. "Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets." International Journal of Oncology International Journal of Oncology 39.5 (2011): 1273-1283.
Chicago
Marimuthu, Chivukula, Alfonso, Moridani, Hagen, and G. Bhat. "Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets." International Journal of Oncology International Journal of Oncology 39 no. 5 (2011): 1273-1283.