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 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.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world
The colony-forming ability of both the colorectal cancer (CRC) and normal colon cell lines was reduced after treatment with genipin, which was consistent with the results of the apoptosis study (Figure 1D)
These results suggested that genipin induced anti-proliferative effects in CRC cells via apoptosis
Summary
The survival rate of patients with CRC has improved, it is lower than that for patient with other types of cancer [1, 2]. A major component of Gardenia jasminoides Ellis fruit, has effects against inflammation, ischemic brain injury, atherosclerosis, platelet aggregation, hyperglycemia, hyperlipidemia, and hypertension [5,6,7]. It has a molecular weight of 226 g/mol (Figure 1A), is white crystalline in structure, and exhibits low cytotoxicity. The potential anti-proliferative activity of genipin in CRC has not yet been investigated
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