The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line

  • Authors:
    • Taka-aki Matsui
    • Yoshihiro Sowa
    • Hiroaki Murata
    • Koichi Takagi
    • Ryoko Nakanishi
    • Shunji Aoki
    • Masayuki Yoshikawa
    • Motomasa Kobayashi
    • Tomoya Sakabe
    • Toshikazu Kubo
    • Toshiyuki Sakai
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijo.31.4.915
  • Pages: 915-922
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Abstract

We previously established a bioassay method to screen for compounds that activate the promoter activity of p21WAF1/CIP1, a potent inhibitor of cyclin-dependent kinases, in a p53-independent manner. As an activator of p21WAF1/CIP1 promoter activity, we isolated cryptolepine (CLP: 5-methyl indolo (2,3b)-quiniine), an indoloquinoline alkaloid, from the traditional Ayurvedic medicinal plant Sida cordifolia. We show here that CLP induces the expression of p21WAF1/CIP1 with growth arrest in p53-mutated human osteosarcoma MG63 cells. Four micromolar of CLP completely inhibited the growth of MG63 cells and caused G2/M-phase arrest. CLP up-regulated the expression of p21WAF1/CIP1 at both mRNA and protein levels in a dose-dependent manner. Using several mutant p21WAF1/CIP1 promoter constructs, we found that the CLP-responsive element is an Sp1 site at -82 relative to the transcription start site of the p21WAF1/CIP1 promoter. These findings suggest that CLP arrests the growth of MG63 cells by activating the p21WAF1/CIP1 promoter through the specific Sp1 site in a p53-independent manner. In addition, CLP-mediated cell cycle arrest was reduced by the knockout of the p21WAF1/CIP1 gene in human colon cancer HCT116 cells, suggesting that the cell cycle arrest by CLP was at least partially mediated through the induction of p21WAF1/CIP1 expression. Although we need further study of chemotherapeutic effect in vivo, these results raise the possibility that CLP might be a suitable chemotherapeutic agent for treatment of osteosarcoma.

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October 2007
Volume 31 Issue 4

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

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Spandidos Publications style
Matsui T, Sowa Y, Murata H, Takagi K, Nakanishi R, Aoki S, Yoshikawa M, Kobayashi M, Sakabe T, Kubo T, Kubo T, et al: The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line. Int J Oncol 31: 915-922, 2007.
APA
Matsui, T., Sowa, Y., Murata, H., Takagi, K., Nakanishi, R., Aoki, S. ... Sakai, T. (2007). The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line. International Journal of Oncology, 31, 915-922. https://doi.org/10.3892/ijo.31.4.915
MLA
Matsui, T., Sowa, Y., Murata, H., Takagi, K., Nakanishi, R., Aoki, S., Yoshikawa, M., Kobayashi, M., Sakabe, T., Kubo, T., Sakai, T."The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line". International Journal of Oncology 31.4 (2007): 915-922.
Chicago
Matsui, T., Sowa, Y., Murata, H., Takagi, K., Nakanishi, R., Aoki, S., Yoshikawa, M., Kobayashi, M., Sakabe, T., Kubo, T., Sakai, T."The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line". International Journal of Oncology 31, no. 4 (2007): 915-922. https://doi.org/10.3892/ijo.31.4.915