Forskolin, a Hedgehog signal inhibitor, inhibits cell proliferation and induces apoptosis in pediatric tumor cell lines

  • Authors:
    • Hiroaki Yamanaka
    • Takaharu Oue
    • Shuichiro Uehara
    • Masahiro Fukuzawa
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/mmr_00000230
  • Pages: 133-139
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Abstract

The Hedgehog (Hh) signaling pathway regulates the development of many organs in mammals. Recent studies have indicated that the activation of the Hh signaling pathway contributes to the growth of various adult cancers. However, little is known about its role in the development of pediatric malignancies. The present study was undertaken to examine the expression and functional involvement of Hh signal transcription factors in pediatric tumor cells in order to determine their potential as therapeutic targets. We utilized real-time RT-PCR to investigate the expression of Glioma-associated oncogene homolog 1 (Gli1) in various pediatric tumor cell lines, including rhabdomyosarcoma, neuroblastoma and hepatoblastoma. The mRNA expression of Gli1 was markedly increased in rhabdomyosarcoma (RMS-YM, RD, RH30) cell lines, and moderately increased in neuroblastoma (NB19) and hepatoblastoma (Huh6) cell lines. The proliferation of these cell lines was dose dependently inhibited by Forskolin, a specific Hh signal inhibitor. In addition, Forskolin-induced growth suppression was associated with the down-regulation of C-Myc. Moreover, the blockade of Hh signaling with Forskolin enhanced cell apoptosis in a dose-dependent manner. These results demonstrated that Hh signal activation frequently occurs in neuroblastoma, hepatoblastoma and rhabdomyosarcoma cell lines. The inhibition of Hh signaling suppressed proliferation and increased apoptosis in these tumor cells. These findings suggest that the Hh signaling pathway plays an important role in tumorigenesis and is a potential molecular target of new treatment strategies for these pediatric malignant tumors.

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January-February 2010
Volume 3 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yamanaka H, Oue T, Uehara S and Fukuzawa M: Forskolin, a Hedgehog signal inhibitor, inhibits cell proliferation and induces apoptosis in pediatric tumor cell lines . Mol Med Rep 3: 133-139, 2010
APA
Yamanaka, H., Oue, T., Uehara, S., & Fukuzawa, M. (2010). Forskolin, a Hedgehog signal inhibitor, inhibits cell proliferation and induces apoptosis in pediatric tumor cell lines . Molecular Medicine Reports, 3, 133-139. https://doi.org/10.3892/mmr_00000230
MLA
Yamanaka, H., Oue, T., Uehara, S., Fukuzawa, M."Forskolin, a Hedgehog signal inhibitor, inhibits cell proliferation and induces apoptosis in pediatric tumor cell lines ". Molecular Medicine Reports 3.1 (2010): 133-139.
Chicago
Yamanaka, H., Oue, T., Uehara, S., Fukuzawa, M."Forskolin, a Hedgehog signal inhibitor, inhibits cell proliferation and induces apoptosis in pediatric tumor cell lines ". Molecular Medicine Reports 3, no. 1 (2010): 133-139. https://doi.org/10.3892/mmr_00000230