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      Curcumin suppresses gastric cancer by inhibiting gastrin‐mediated acid secretion

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          Abstract

          Hyperacidity in the stomach is known to promote the progression of gastric cancer. The plant‐derived chemotherapeutic curcumin is used to treat gastric cancer. The objective of this study was to investigate whether curcumin regulates gastrin‐mediated acid secretion in suppressing gastric cancer. Gastric cancer cells were treated with 25 μ m curcumin, followed by Annexin V/propidium iodide double‐staining assay to evaluate cell apoptosis. Western blot analysis was used to analyze caspase‐3 expression in response to curcumin treatment. Gastrin levels in culture medium were also monitored. Mice bearing gastric cancers were treated with curcumin, followed by analysis of tumor caspase‐3 expression, gastric acid pH, and gastric secretion in serum. Curcumin prominently inhibited gastric cancer cell proliferation and promoted cell apoptosis. Caspase‐3 was upregulated by curcumin treatment. Curcumin also reduced gastrin secretion. Curcumin dramatically inhibited tumor growth, increased gastric pH, and reduced gastric secretion. In gastric cancer, curcumin suppresses gastrin‐mediated acid secretion, which inhibits gastric cancer progression.

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          Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway

          Ruzhen Zheng, Qinghua Deng, Yuehua Liu … (2017)
          Background Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/β-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. Material/Methods We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay. Results Curcumin markedly impaired tumor cell viability and induced apoptosis in vitro. Curcumin significantly suppressed the levels of Wnt3a, LRP6, phospho-LRP6, β-catenin, phospho-β-catenin, C-myc, and survivin. Xenograft growth in vivo was inhibited and the target genes of Wnt/β-catenin signaling were also reduced by curcumin treatment. Conclusions Curcumin exerts anti-proliferative and pro-apoptotic effect in gastric cancer cells and in a xenograft model. Inhibition of the Wnt/β-catenin signaling pathway and the subsequently reduced expression of Wnt target genes show potential as a newly-identified molecular mechanism of curcumin treatment.
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            Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression.

            Nan Liu, Jian Wang, Mao-Sheng Cheng … (2009)
            Curcumin (diferuloylmethane), is a natural chemopreventive agent known to inhibit the proliferation of several cancer cell lines. It has been previously demonstrated that curcumin is a potent inhibitor of EGF-receptor (EGFR) tyrosine kinase, but its inhibitive effect on p21-activated kinase 1 (PAK1), a downstream protein of EGFR, has not been defined. In this paper we found that curcumin repressed the expression of HER2 and inhibited the kinase activity of PAK1 without affecting its expression. Silencing HER2 in gastric cancer cells showed that even if PAK1 activity was transiently strengthened by EGF, curcumin still had a strong inhibitive effect. It should be emphasized that kinase assay in vitro showed that curcumin could act as an ATP-competitive inhibitor, which was supported by computer-aided molecular modeling. Curcumin also downregulated the mRNA and the protein expression of cyclin D1 and suppressed transition of the cells from G(1) to S phase. Therefore, curcumin inhibited the proliferation and invasion of gastric cancer cells. Overall, these results provided novel insights into the mechanisms of curcumin inhibition of gastric cancer cell growth and potential therapeutic strategies for gastric cancer.
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              Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor.

              Liang-Liang Yu, Jia-Guo Wu, Ning Dai … (2011)
              Gastric cancer remains one of the major health problems worldwide. Chemotherapy is an important therapeutic modality for gastric cancer, but the success rate of this treatment is limited because of chemoresistance. The ubiquitously expressed transcription factor NF-κB has been suggested to be associated with chemoresistance of gastric cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance to chemotherapeutics are needed for the treatment of gastric cancer. Curcumin, a component of turmeric, is one such agent that has been shown to suppress NF-κB and increase the efficacy of chemotherapy. In this study, we investigated whether curcumin can reverse chemoresistance by downregulating NF-κB in human gastric cancer cells. SGC-7901 human gastric cancer cells was treated with chemotherapeutics (etoposide and doxorubicin) or by combined application of curcumin and chemotherapeutics. The viability of SGC-7901 cells was measured by MTT assay. Apoptosis of SGC-7901 cells was detected using the TUNEL and Annexin V/PI methods. The protein levels of NF-κB were analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein levels of p-IκBα, Bcl-2 and Bcl-xL were analyzed by Western blotting. The chemotherapeutics (etoposide and doxorubicin) suppressed the growth of SGC-7901 cells, in a time-dose-dependent manner. Use of curcumin in addition to these agents can suppress cell growth further (inhibitory rate: doxorubicin vs. doxorubicin + curcumin, 33% vs. 45%, p<0.05; etoposide vs. etoposide + curcumin, 35% vs. 48%, p<0.05). Furthermore, chemotherapeutics induced apoptosis of SGC-7901 cells and activated NF-κB. The combination of curcumin and chemotherapeutics induced apoptosis of SGC-7901 cells further, attenuated the activation of NF-κB, and reduced expression of the NF-κB-regulated anti-apoptotic gene products Bcl-2 and Bcl-xL. Curcumin potentiates the antitumor effects of chemotherapeutics in gastric cancer by suppressing NF-κB and NF-κB-regulated anti-apoptotic genes.
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                Author and article information

                Contributors
                Ling Teng: tlandqjy@126.com
                Journal
                Journal ID (nlm-ta): FEBS Open Bio
                Journal ID (iso-abbrev): FEBS Open Bio
                Journal ID (doi): 10.1002/(ISSN)2211-5463
                Journal ID (publisher-id): FEB4
                Title: FEBS Open Bio
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2211-5463
                Publication date (Electronic): 21 June 2017
                Publication date Collection: August 2017
                Volume: 7
                Issue: 8 ( doiID: 10.1111/feb4.2017.7.issue-8 )
                Pages: 1078-1084
                Affiliations
                [ 1 ] Department of Gerontology, Affiliated Second Hospital Mudanjiang Medical University China
                [ 2 ] Department of Quality Control, Affiliated Second Hospital Mudanjiang Medical University China
                [ 3 ] Department of Pathology, Affiliated Second Hospital Mudanjiang Medical University China
                Author notes
                [*] [* ] Correspondence

                L. Teng, Department of Gerontology, Affiliated Second Hospital, Mudanjiang Medical University, No.15 East Xiao Yun Street, Mudangjiang 157009, China

                E‐mail: tlandqjy@ 123456126.com

                Article
                Publisher ID: FEB412237
                DOI: 10.1002/2211-5463.12237
                PMC ID: 5537064
                SO-VID: c7618a14-8fcc-4c8d-a56b-5cf1ce89c56b
                Copyright © © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 02 March 2017
                Date revision received : 15 April 2017
                Date accepted : 18 April 2017
                Page count
                Figures: 5, Tables: 0, Pages: 7, Words: 4382
                Categories
                Subject: Research Article
                Subject: Research Articles
                Custom metadata
                source-schema-version-number 2.0
                component-id feb412237
                cover-date August 2017
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:31.07.2017

                Keywords: acid secretion,curcumin,gastric cancer,gastrin
                Data availability:
                Keywords: acid secretion, curcumin, gastric cancer, gastrin

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