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      Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling

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          Abstract

          Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.

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          Molecular characterization of the tumor microenvironment in breast cancer.

          Minna Allinen, Rameen Beroukhim, Li Cai … (2004)
          Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.
          Article 0 comments Cited 367 times – based on 0 reviews     Review now
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            Pharmacology of Curcuma longa.

            H P Ammon, M A Wahl (1991)
            The data reviewed indicate that extracts of Curcuma longa exhibit anti-inflammatory activity after parenteral application in standard animal models used for testing anti-inflammatory activity. It turned out that curcumin and the volatile oil are at least in part responsible for this action. It appears that when given orally, curcumin is far less active than after i.p. administration. This may be due to poor absorption, as discussed. Data on histamine-induced ulcers are controversial, and studies on the secretory activity (HCl, pepsinogen) are still lacking. In vitro, curcumin exhibited antispasmodic activity. Since there was a protective effect of extracts of Curcuma longa on the liver and a stimulation of bile secretion in animals, Curcuma longa has been advocated for use in liver disorders. Evidence for an effect on liver disease in humans is not yet available. From the facts that after oral application only traces of curcumin were found in the blood and that, on the other hand, most of the curcumin is excreted via the faeces it may be concluded that curcumin is absorbed poorly by the gastrointestinal tract and/or underlies presystemic transformation. Systemic effects therefore seem to be questionable after oral application except that they occur at very low concentrations of curcumin. This does not exclude a local action in the gastrointestinal tract.
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              New signals from the invasive front.

              Gerhard Christofori (2006)
              Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumours. Of all the processes involved in carcinogenesis, local invasion and the formation of metastases are clinically the most relevant, but they are the least well understood at the molecular level. Revealing their mechanisms is one of the main challenges for exploratory and applied cancer research. Recent experimental progress has identified a number of molecular pathways and cellular mechanisms that underlie the multistage process of metastasis formation: these include tumour invasion, tumour-cell dissemination through the bloodstream or the lymphatic system, colonization of distant organs and, finally, fatal outgrowth of metastases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Oncol
                Journal ID (iso-abbrev): Int. J. Oncol
                Journal ID (publisher-id): IJO
                Title: International Journal of Oncology
                Publisher: D.A. Spandidos
                ISSN (Print): 1019-6439
                ISSN (Electronic): 1791-2423
                Publication date Collection: December 2015
                Publication date (Electronic): 13 October 2015
                Publication date PMC-release: 13 October 2015
                Volume: 47
                Issue: 6
                Pages: 2064-2072
                Affiliations
                [1 ]Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
                [2 ]Department of Urology, Tongji Medical College Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
                [3 ]School of Life Science and Technology, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
                Author notes
                Correspondence to: Dr Dalin He, Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi 710061, P.R. China, E-mail: dlhe2010@ 123456163.com
                Article
                Publisher ID: ijo-47-06-2064
                DOI: 10.3892/ijo.2015.3202
                PMC ID: 4665143
                PubMed ID: 26499200
                SO-VID: 7ba175a2-0f8f-4107-9bfd-5a4db3c56db2
                Copyright © Copyright: © Du et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, 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.

                History
                Date received : 02 August 2015
                Date accepted : 25 September 2015
                Categories
                Subject: Articles

                Keywords: curcumin,cancer-associated fibroblasts,monoamine oxidase a/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling,prostate cancer,invasion
                Data availability:
                Keywords: curcumin, cancer-associated fibroblasts, monoamine oxidase a/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling, prostate cancer, invasion

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