Andrographolide induces degradation of mutant p53 via activation of Hsp70

  • Authors:
    • Hirofumi Sato
    • Masatsugu Hiraki
    • Takushi Namba
    • Noriyuki Egawa
    • Koichi Baba
    • Tomokazu Tanaka
    • Hirokazu Noshiro
  • View Affiliations

  • Published online on: May 22, 2018     https://doi.org/10.3892/ijo.2018.4416
  • Pages: 761-770
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Abstract

The tumor suppressor gene p53 encodes a transcription factor that regulates various cellular functions, including DNA repair, apoptosis and cell cycle progression. Approximately half of all human cancers carry mutations in p53 that lead to loss of tumor suppressor function or gain of functions that promote the cancer phenotype. Thus, targeting mutant p53 as an anticancer therapy has attracted considerable attention. In the current study, a small-molecule screen identified andrographlide (ANDRO) as a mutant p53 suppressor. The effects of ANDRO, a small molecule isolated from the Chinese herb Andrographis paniculata, on tumor cells carrying wild-type or mutant p53 were examined. ANDRO suppressed expression of mutant p53, induced expression of the cyclin-dependent kinase inhibitor p21 and pro-apoptotic proteins genes, and inhibited the growth of cancer cells harboring mutant p53. ANDRO also induced expression of the heat-shock protein (Hsp70) and increased binding between Hsp70 and mutant p53 protein, thus promoting proteasomal degradation of p53. These results provide novel insights into the mechanisms regulating the function of mutant p53 and suggest that activation of Hsp70 may be a new strategy for the treatment of cancers harboring mutant p53.
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August-2018
Volume 53 Issue 2

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

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Spandidos Publications style
Sato H, Hiraki M, Namba T, Egawa N, Baba K, Tanaka T and Noshiro H: Andrographolide induces degradation of mutant p53 via activation of Hsp70. Int J Oncol 53: 761-770, 2018.
APA
Sato, H., Hiraki, M., Namba, T., Egawa, N., Baba, K., Tanaka, T., & Noshiro, H. (2018). Andrographolide induces degradation of mutant p53 via activation of Hsp70. International Journal of Oncology, 53, 761-770. https://doi.org/10.3892/ijo.2018.4416
MLA
Sato, H., Hiraki, M., Namba, T., Egawa, N., Baba, K., Tanaka, T., Noshiro, H."Andrographolide induces degradation of mutant p53 via activation of Hsp70". International Journal of Oncology 53.2 (2018): 761-770.
Chicago
Sato, H., Hiraki, M., Namba, T., Egawa, N., Baba, K., Tanaka, T., Noshiro, H."Andrographolide induces degradation of mutant p53 via activation of Hsp70". International Journal of Oncology 53, no. 2 (2018): 761-770. https://doi.org/10.3892/ijo.2018.4416