Cargando…
Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein
Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangioca...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520142/ https://www.ncbi.nlm.nih.gov/pubmed/36154723 http://dx.doi.org/10.1177/15347354221124861 |
_version_ | 1784799558735233024 |
---|---|
author | Kaewmeesri, Putthaporn Pocasap, Piman Kukongviriyapan, Veerapol Prawan, Auemduan Kongpetch, Sarinya Senggunprai, Laddawan |
author_facet | Kaewmeesri, Putthaporn Pocasap, Piman Kukongviriyapan, Veerapol Prawan, Auemduan Kongpetch, Sarinya Senggunprai, Laddawan |
author_sort | Kaewmeesri, Putthaporn |
collection | PubMed |
description | Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells. To investigate this, the role of Src in regulating metastasis behavior of CCA cells and the effect of cucurbitacin B on Src-mediated metastatic phenotype of these cells were determined. The results showed that activation of Src significantly enhanced the migratory and invasive abilities of CCA cells. Molecular analysis revealed that Src-facilitated metastasis behavior of CCA cells occurred by modifying expression of a wide range of metastasis-related genes in the cells. Consistent with gene expression results, activation of Src significantly induced the protein expression of 2 important metastasis-associated molecules, MMP-9 and VEGF. Cucurbitacin B markedly suppressed activation of Src and its key effector, FAK. As a consequence, the alteration of expression profiles of metastasis-associated genes induced by Src activator in CCA cells was diminished by cucurbitacin B treatment. The compound also down-regulated Src-induced expression of MMP-9 and VEGF proteins in the cells. Moreover, molecular docking analysis revealed that cucurbitacin B could interact with Src kinase domain and possibly restrain the kinase from being activated by hindering the ATP binding. In conclusion, cucurbitacin B exhibited anti-metastatic property in CCA cells via negatively influencing Src and Src-related oncogenic signaling. This compound may therefore be a potential therapeutic drug for further development as an anti-Src agent for treatment of metastatic CCA. |
format | Online Article Text |
id | pubmed-9520142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-95201422022-09-30 Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein Kaewmeesri, Putthaporn Pocasap, Piman Kukongviriyapan, Veerapol Prawan, Auemduan Kongpetch, Sarinya Senggunprai, Laddawan Integr Cancer Ther Research Article Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells. To investigate this, the role of Src in regulating metastasis behavior of CCA cells and the effect of cucurbitacin B on Src-mediated metastatic phenotype of these cells were determined. The results showed that activation of Src significantly enhanced the migratory and invasive abilities of CCA cells. Molecular analysis revealed that Src-facilitated metastasis behavior of CCA cells occurred by modifying expression of a wide range of metastasis-related genes in the cells. Consistent with gene expression results, activation of Src significantly induced the protein expression of 2 important metastasis-associated molecules, MMP-9 and VEGF. Cucurbitacin B markedly suppressed activation of Src and its key effector, FAK. As a consequence, the alteration of expression profiles of metastasis-associated genes induced by Src activator in CCA cells was diminished by cucurbitacin B treatment. The compound also down-regulated Src-induced expression of MMP-9 and VEGF proteins in the cells. Moreover, molecular docking analysis revealed that cucurbitacin B could interact with Src kinase domain and possibly restrain the kinase from being activated by hindering the ATP binding. In conclusion, cucurbitacin B exhibited anti-metastatic property in CCA cells via negatively influencing Src and Src-related oncogenic signaling. This compound may therefore be a potential therapeutic drug for further development as an anti-Src agent for treatment of metastatic CCA. SAGE Publications 2022-09-26 /pmc/articles/PMC9520142/ /pubmed/36154723 http://dx.doi.org/10.1177/15347354221124861 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Kaewmeesri, Putthaporn Pocasap, Piman Kukongviriyapan, Veerapol Prawan, Auemduan Kongpetch, Sarinya Senggunprai, Laddawan Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title | Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title_full | Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title_fullStr | Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title_full_unstemmed | Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title_short | Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein |
title_sort | anti-metastatic potential of natural triterpenoid cucurbitacin b against cholangiocarcinoma cells by targeting src protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520142/ https://www.ncbi.nlm.nih.gov/pubmed/36154723 http://dx.doi.org/10.1177/15347354221124861 |
work_keys_str_mv | AT kaewmeesriputthaporn antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein AT pocasappiman antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein AT kukongviriyapanveerapol antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein AT prawanauemduan antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein AT kongpetchsarinya antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein AT senggunprailaddawan antimetastaticpotentialofnaturaltriterpenoidcucurbitacinbagainstcholangiocarcinomacellsbytargetingsrcprotein |