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Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide; however, there is still a lack of effective clinical anti-CRC agents. Naturally-occurring compounds have been considered a potentially valuable source of new antitumorigenic agents. Involucrasin A, a novel natural mol...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157355/ https://www.ncbi.nlm.nih.gov/pubmed/37153032 http://dx.doi.org/10.3892/ol.2023.13804 |
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author | Wei, Chengming Du, Jingjing Shen, Yunfu Wang, Zi Lin, Qianyu Chen, Junhe Zhang, Fuming Lin, Wanjun Wang, Zhibin Yang, Zhuya Ma, Wenzhe |
author_facet | Wei, Chengming Du, Jingjing Shen, Yunfu Wang, Zi Lin, Qianyu Chen, Junhe Zhang, Fuming Lin, Wanjun Wang, Zhibin Yang, Zhuya Ma, Wenzhe |
author_sort | Wei, Chengming |
collection | PubMed |
description | Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide; however, there is still a lack of effective clinical anti-CRC agents. Naturally-occurring compounds have been considered a potentially valuable source of new antitumorigenic agents. Involucrasin A, a novel natural molecule, was isolated from Shuteria involucrata (Wall.) Wight & Arn by our team. In the present study, the anticancer activity of involucrasin A in HCT-116 CRC cells was evaluated. Firstly, the anti-proliferative effect of involucrasin A on HCT-116 cells was analyzed by sulforhodamine B and colony formation assays. The results revealed that involucrasin A exhibited a potent inhibitory effect on HCT-116 CRC cell proliferation in vitro. Subsequently, flow cytometry and western blotting indicated that involucrasin A induced apoptosis and upregulated the expression levels of apoptosis-related proteins, such as cleaved-caspase 6 and cleaved-caspase 9, in a dose-dependent manner. Mechanistically, involucrasin A significantly inhibited the phosphorylation of Akt and murine double minute 2 homologue (MDM2), which resulted in increased intracellular levels of p53. This was reversed by exogenous expression of the constitutively active form of Akt. Similarly, either knocking out p53 or knocking down Bax abrogated involucrasin A-induced proliferation inhibition and apoptosis. Together, the present study indicated that involucrasin A exerts antitumorigenic activities via modulating the Akt/MDM2/p53 pathway in HCT-116 CRC cells, and it is worthy of further exploration in preclinical and clinical trials. |
format | Online Article Text |
id | pubmed-10157355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-101573552023-05-05 Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway Wei, Chengming Du, Jingjing Shen, Yunfu Wang, Zi Lin, Qianyu Chen, Junhe Zhang, Fuming Lin, Wanjun Wang, Zhibin Yang, Zhuya Ma, Wenzhe Oncol Lett Articles Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide; however, there is still a lack of effective clinical anti-CRC agents. Naturally-occurring compounds have been considered a potentially valuable source of new antitumorigenic agents. Involucrasin A, a novel natural molecule, was isolated from Shuteria involucrata (Wall.) Wight & Arn by our team. In the present study, the anticancer activity of involucrasin A in HCT-116 CRC cells was evaluated. Firstly, the anti-proliferative effect of involucrasin A on HCT-116 cells was analyzed by sulforhodamine B and colony formation assays. The results revealed that involucrasin A exhibited a potent inhibitory effect on HCT-116 CRC cell proliferation in vitro. Subsequently, flow cytometry and western blotting indicated that involucrasin A induced apoptosis and upregulated the expression levels of apoptosis-related proteins, such as cleaved-caspase 6 and cleaved-caspase 9, in a dose-dependent manner. Mechanistically, involucrasin A significantly inhibited the phosphorylation of Akt and murine double minute 2 homologue (MDM2), which resulted in increased intracellular levels of p53. This was reversed by exogenous expression of the constitutively active form of Akt. Similarly, either knocking out p53 or knocking down Bax abrogated involucrasin A-induced proliferation inhibition and apoptosis. Together, the present study indicated that involucrasin A exerts antitumorigenic activities via modulating the Akt/MDM2/p53 pathway in HCT-116 CRC cells, and it is worthy of further exploration in preclinical and clinical trials. D.A. Spandidos 2023-04-12 /pmc/articles/PMC10157355/ /pubmed/37153032 http://dx.doi.org/10.3892/ol.2023.13804 Text en Copyright: © Wei et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wei, Chengming Du, Jingjing Shen, Yunfu Wang, Zi Lin, Qianyu Chen, Junhe Zhang, Fuming Lin, Wanjun Wang, Zhibin Yang, Zhuya Ma, Wenzhe Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title | Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title_full | Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title_fullStr | Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title_full_unstemmed | Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title_short | Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway |
title_sort | anticancer effect of involucrasin a on colorectal cancer cells by modulating the akt/mdm2/p53 pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157355/ https://www.ncbi.nlm.nih.gov/pubmed/37153032 http://dx.doi.org/10.3892/ol.2023.13804 |
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