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

    Research output: Contribution to journalArticlepeer-review

    31 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

    Bibliographical note

    Funding Information:
    This work was supported by grant from the National Research Foundation (NRF) of Korea funded by the Korean government (MSIP) [NRF-2017R1A2B2011684] and [NRF-2015R1D1A1A01058303].

    Publisher Copyright:
    © Kim et al.

    Keywords

    • GLI1
    • Genipin
    • Hedgehog pathway
    • NOXA
    • Ubiquitin

    ASJC Scopus subject areas

    • Oncology

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