Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway

  • Authors:
    • Nobumasa Takagaki
    • Yoshihiro Sowa
    • Teruki Oki
    • Ryoko Nakanishi
    • Shingo Yogosawa
    • Toshiyuki Sakai
  • View Affiliations

  • Published online on: January 1, 2005     https://doi.org/10.3892/ijo.26.1.185
  • Pages: 185-189
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Abstract

Apigenin, a common dietary flavonoid, has been shown to induce cell growth-inhibition and cell cycle arrest in many cancer cell lines. One important effect of apigenin is to increase the stability of the tumor suppressor p53 in normal cells. Therefore, apigenin is expected to play a large role in cancer prevention by modifying the effects of p53 protein. However, the mechanisms of apigenin's effects on p53-mutant cancer cells have not been revealed yet. We assessed the influence of apigenin on cell growth and the cell cycle in p53-mutant cell lines. Treatment with apigenin resulted in growth-inhibition and G2/M phase arrest in two p53-mutant cancer cell lines, HT-29 and MG63. These effects were associated with a marked increase in the protein expression of p21/WAF1. We have shown that p21/WAF1 mRNA expression was also markedly increased by treatment with apigenin in a dose- and time-dependent manner. However, we could not detect p21/WAF1 promoter activity following treatment with apigenin. Similarly, promoter activity from pG13-Luc, a p53-responsive promoter plasmid, was not activated by treatment with apigenin with or without p53 protein expression. These results suggest that there is a p53-independent pathway for apigenin in p53-mutant cell lines, which induces p21/WAF1 expression and growth-inhibition. Apigenin may be a useful chemopreventive agent not only in wild-type p53 status, but also in cancer with mutant p53.

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January 2005
Volume 26 Issue 1

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

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Spandidos Publications style
Takagaki N, Sowa Y, Oki T, Nakanishi R, Yogosawa S and Sakai T: Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway. Int J Oncol 26: 185-189, 2005
APA
Takagaki, N., Sowa, Y., Oki, T., Nakanishi, R., Yogosawa, S., & Sakai, T. (2005). Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway. International Journal of Oncology, 26, 185-189. https://doi.org/10.3892/ijo.26.1.185
MLA
Takagaki, N., Sowa, Y., Oki, T., Nakanishi, R., Yogosawa, S., Sakai, T."Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway". International Journal of Oncology 26.1 (2005): 185-189.
Chicago
Takagaki, N., Sowa, Y., Oki, T., Nakanishi, R., Yogosawa, S., Sakai, T."Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway". International Journal of Oncology 26, no. 1 (2005): 185-189. https://doi.org/10.3892/ijo.26.1.185