Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway

Bo Ram Kim, Yoon A. Jeong, Yoo Jin Na, Seong Hye Park, Min Jee Jo, Jung Lim Kim, Soyeon Jeong, Suk Young Lee, Hong Jun Kim, Sang Cheul Oh, Dae Hee Lee

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15 Citations (Scopus)

Abstract

Genipin, a major component of Gardenia jasminoides Ellis fruit, has been shown to inhibit the growth of gastric, prostate, and breast cancers. However, the antiproliferative activity of genipin in colorectal cancer (CRC) has not been characterized. Herein, we demonstrated that genipin inhibits the proliferation of CRC cells and that genipin suppressed the Hedgehog pathway. Further investigation showed that p53 and NOXA protein levels were increased during inhibition of Hedgehog pathway-mediated apoptosis in CRC cells. We also showed that p53 modulated the expression of NOXA during genipin-induced apoptosis, and suppression via SMO also played a role in this process. Subsequently, GLI1 was ubiquitinated by the E3 ligase PCAF. In a xenograft tumor model, genipin suppressed tumor growth, which was also associated with Hedgehog inactivation. Taken together, these results suggest that genipin induces apoptosis through the Hedgehog signaling pathway by suppressing p53. These findings reveal a novel regulatory mechanism involving Hedgehog/p53/NOXA signaling in the modulation of CRC cell apoptosis and tumorforming defects.

Original languageEnglish
Pages (from-to)101952-101964
Number of pages13
JournalOncotarget
Volume8
Issue number60
DOIs
Publication statusPublished - 2017 Jan 1

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Keywords

  • Genipin
  • GLI1
  • Hedgehog pathway
  • NOXA
  • Ubiquitin

ASJC Scopus subject areas

  • Oncology

Cite this

Kim, B. R., Jeong, Y. A., Na, Y. J., Park, S. H., Jo, M. J., Kim, J. L., Jeong, S., Lee, S. Y., Kim, H. J., Oh, S. C., & Lee, D. H. (2017). Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway. Oncotarget, 8(60), 101952-101964. https://doi.org/10.18632/oncotarget.21882