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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...

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Autores principales: Wei, Chengming, Du, Jingjing, Shen, Yunfu, Wang, Zi, Lin, Qianyu, Chen, Junhe, Zhang, Fuming, Lin, Wanjun, Wang, Zhibin, Yang, Zhuya, Ma, Wenzhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
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.
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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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