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Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway

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...

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Autores principales: Kim, Bo Ram, Jeong, Yoon A., Na, Yoo Jin, Park, Seong Hye, Jo, Min Jee, Kim, Jung Lim, Jeong, Soyeon, Lee, Suk-Young, Kim, Hong Jun, Oh, Sang Cheul, Lee, Dae-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731927/
https://www.ncbi.nlm.nih.gov/pubmed/29254217
http://dx.doi.org/10.18632/oncotarget.21882
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author Kim, Bo Ram
Jeong, Yoon A.
Na, Yoo Jin
Park, Seong Hye
Jo, Min Jee
Kim, Jung Lim
Jeong, Soyeon
Lee, Suk-Young
Kim, Hong Jun
Oh, Sang Cheul
Lee, Dae-Hee
author_facet Kim, Bo Ram
Jeong, Yoon A.
Na, Yoo Jin
Park, Seong Hye
Jo, Min Jee
Kim, Jung Lim
Jeong, Soyeon
Lee, Suk-Young
Kim, Hong Jun
Oh, Sang Cheul
Lee, Dae-Hee
author_sort Kim, Bo Ram
collection PubMed
description 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.
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spelling pubmed-57319272017-12-17 Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway Kim, Bo Ram Jeong, Yoon A. Na, Yoo Jin Park, Seong Hye Jo, Min Jee Kim, Jung Lim Jeong, Soyeon Lee, Suk-Young Kim, Hong Jun Oh, Sang Cheul Lee, Dae-Hee Oncotarget Research Paper 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. Impact Journals LLC 2017-10-16 /pmc/articles/PMC5731927/ /pubmed/29254217 http://dx.doi.org/10.18632/oncotarget.21882 Text en Copyright: © 2017 Kim et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kim, Bo Ram
Jeong, Yoon A.
Na, Yoo Jin
Park, Seong Hye
Jo, Min Jee
Kim, Jung Lim
Jeong, Soyeon
Lee, Suk-Young
Kim, Hong Jun
Oh, Sang Cheul
Lee, Dae-Hee
Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title_full Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title_fullStr Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title_full_unstemmed Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title_short Genipin suppresses colorectal cancer cells by inhibiting the Sonic Hedgehog pathway
title_sort genipin suppresses colorectal cancer cells by inhibiting the sonic hedgehog pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731927/
https://www.ncbi.nlm.nih.gov/pubmed/29254217
http://dx.doi.org/10.18632/oncotarget.21882
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