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Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma
Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203149/ https://www.ncbi.nlm.nih.gov/pubmed/30272283 http://dx.doi.org/10.3892/ijo.2018.4569 |
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author | Zhang, Chengke Hao, Yingtao Wu, Licun Dong, Xiaopeng Jiang, Ning Cong, Bo Liu, Jiang Zhang, Wen Tang, Dongqi De Perrot, Marc Zhao, Xiaogang |
author_facet | Zhang, Chengke Hao, Yingtao Wu, Licun Dong, Xiaopeng Jiang, Ning Cong, Bo Liu, Jiang Zhang, Wen Tang, Dongqi De Perrot, Marc Zhao, Xiaogang |
author_sort | Zhang, Chengke |
collection | PubMed |
description | Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin-induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)-mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase-independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM. |
format | Online Article Text |
id | pubmed-6203149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-62031492018-11-09 Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma Zhang, Chengke Hao, Yingtao Wu, Licun Dong, Xiaopeng Jiang, Ning Cong, Bo Liu, Jiang Zhang, Wen Tang, Dongqi De Perrot, Marc Zhao, Xiaogang Int J Oncol Articles Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin-induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)-mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase-independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM. D.A. Spandidos 2018-09-21 /pmc/articles/PMC6203149/ /pubmed/30272283 http://dx.doi.org/10.3892/ijo.2018.4569 Text en Copyright: © Zhang et al. 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 Zhang, Chengke Hao, Yingtao Wu, Licun Dong, Xiaopeng Jiang, Ning Cong, Bo Liu, Jiang Zhang, Wen Tang, Dongqi De Perrot, Marc Zhao, Xiaogang Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title | Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title_full | Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title_fullStr | Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title_full_unstemmed | Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title_short | Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
title_sort | curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203149/ https://www.ncbi.nlm.nih.gov/pubmed/30272283 http://dx.doi.org/10.3892/ijo.2018.4569 |
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