Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening

  • Authors:
    • Su-Jin Lee
    • Youn-Sang Jung
    • Sun-Hye Lee
    • Hye-Young Chung
    • Bum-Joon Park
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/ijo_00000294
  • Pages: 1637-1643
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Abstract

The strong tumor suppressor p53 shows loss of function in large portion of human cancer. In addition to genetic mutation, biological function of p53 is suppressed by signaling distortion or elevated expression of p53 inhibitors (such as overexpression of MDM2 or deletion of p14/ARF). In this study, we demonstrate that K-Ras, a frequently altered oncogene in human cancers including pancreatic cancer (about 80%), colon cancer (45%) and lung cancer (45%), suppresses p53. Based on this fact, we perform Western blot analysis-based chemical screening to isolate a K-Ras-specific activator of p53. From 117 kinds of chemicals (34 kinds of natural compounds that are obtained from herbal plants, 53 kinds of flavonoid, and 31 kinds of phenolic compounds), we find that quercetin works as an activator of p53 in K-Ras mutated cells but not in wild-type cells. Treatment with quercetin can induce p53 target genes such as PUMA and p21. These results suggest that although quercetin has limitations for use as a therapeutic drug due to its broad effects, specific function of it on K-Ras-p53 may be useful for K-Ras-induced cancer prevention and therapy through further development.

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June 2009
Volume 34 Issue 6

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

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Spandidos Publications style
Lee S, Jung Y, Lee S, Chung H and Park B: Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening. Int J Oncol 34: 1637-1643, 2009
APA
Lee, S., Jung, Y., Lee, S., Chung, H., & Park, B. (2009). Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening. International Journal of Oncology, 34, 1637-1643. https://doi.org/10.3892/ijo_00000294
MLA
Lee, S., Jung, Y., Lee, S., Chung, H., Park, B."Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening". International Journal of Oncology 34.6 (2009): 1637-1643.
Chicago
Lee, S., Jung, Y., Lee, S., Chung, H., Park, B."Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening". International Journal of Oncology 34, no. 6 (2009): 1637-1643. https://doi.org/10.3892/ijo_00000294