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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...

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Autores principales: Zhang, Chengke, Hao, Yingtao, Wu, Licun, Dong, Xiaopeng, Jiang, Ning, Cong, Bo, Liu, Jiang, Zhang, Wen, Tang, Dongqi, De Perrot, Marc, Zhao, Xiaogang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
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.
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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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