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Article Publish Status: FREE
Abstract Title:

Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway.

Abstract Source:

Oncotarget. 2017 Nov 24 ;8(60):101952-101964. Epub 2017 Oct 16. PMID: 29254217

Abstract Author(s):

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

Article Affiliation:

Bo Ram Kim

Abstract:

Genipin, a major component ofEllis fruit, has been shown to inhibit the growth of gastric, prostate, and breast cancers. However, the anti-proliferative 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 tumor-forming defects.

Study Type : Animal Study, In Vitro Study

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