Genipin Suppresses Colorectal Cancer Cells by Inhibiting the Sonic Hedgehog Pathway

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 20

PMID 29254217

Citations 16

Authors

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

Affiliations

Soon will be listed here.

Abstract

Genipin, a major component of Ellis 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.

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