Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention

  • Authors:
    • Suresh Guruswamy
    • Chinthalapally V. Rao
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000418
  • Pages: 1037-1043
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Abstract

Progression of colon cancer is associated with the up-regulation of cyclooxygenase-2 (COX-2) and hydroxymethyl glutaryl CoA reductase (HMG-R). Clinical and preclinical evidence shows that a combination of COX-2 and HMG-R inhibitors provide additive/synergistic chemopreventive effects against colorectal cancer. However, the mechanism by which statins and NSAIDs inhibit cancer growth is not yet fully understood. We aimed to identify critical molecules and signal pathways modulated by a combination of lovastatin and celecoxib in the human HCT-116 colon cancer cell line. HCT-116 cells were exposed to 50 µM celecoxib, 25 µM lovastatin or a combination of both to assess their effect in modulating caveolin-1 expression and its down-stream signaling pathways. Our results suggest that a combination of lovastatin and/or celecoxib suppressed caveolin-1 expression and membrane localization profoundly when compared to either agent alone. Lovastatin and/or celecoxib also inhibited caveolin-1-dependent cell survival signals mediated through Akt activation as well as its down-stream effectors such as phosphorylated ERK and STAT3 in HCT-116 cells. Treatment with lovastatin or celecoxib decreased the levels of cyclin D1, CDK2, pRb and E2F1, while the combination treatment showed more pronounced suppression. In addition, lovastatin and celecoxib also decreased the amount of cholesterol rich cytoplasmic lipid bodies (storehouses of esteridied arachidonates) by 80%, while the combination showed a complete inhibition. Overall, our data suggest that a combination of COX-2 and HMG-R inhibitors synergistically inhibits caveolin-1 and its associated signaling pathways.

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November 2009
Volume 35 Issue 5

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

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Spandidos Publications style
Guruswamy S and Rao CV: Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention. Int J Oncol 35: 1037-1043, 2009.
APA
Guruswamy, S., & Rao, C.V. (2009). Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention. International Journal of Oncology, 35, 1037-1043. https://doi.org/10.3892/ijo_00000418
MLA
Guruswamy, S., Rao, C. V."Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention". International Journal of Oncology 35.5 (2009): 1037-1043.
Chicago
Guruswamy, S., Rao, C. V."Synergistic effects of lovastatin and celecoxib on caveolin-1 and its down-stream signaling molecules: Implications for colon cancer prevention". International Journal of Oncology 35, no. 5 (2009): 1037-1043. https://doi.org/10.3892/ijo_00000418