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      Curcumin inhibits proliferation of gastric cancer cells by impairing ATP-sensitive potassium channel opening

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          Abstract

          Background

          This study was aimed to investigate whether ATP-sensitive potassium channel (K ATP) is involved in curcumin’s anti-proliferative effects against gastric cancer.

          Methods

          In an in vitro study, gastric cancer cell line SGC-7901 was treated with curcumin at serial concentrations and co-administrated with the K ATP opener, diazoxide. The effect of curcumin and diazoxide on proliferation were assessed by MTT assay. Mitochondrial membrane potential (MMP) was studied by flow cytometry detection of rhodamine 123 staining. Apoptosis was evaluated by flow cytometry detection of Annexin V propidium iodide double staining. In an in vivo study, SGC-7901 cells were planted into nude mice as xenografts. Animals were treated with curcumin co-administered with diazoxide. Tumor volume and tumor weight were observed.

          Results

          Curcumin incubation significantly induced loss of MMP in SGC-7901 cells in a dose- dependent manner ( P < 0.05); the cell apoptotic rate also dramatically increased after curcumin incubation in a dose-dependent manner ( P < 0.05). After co-administration with diazoxide, however, we found that both the MMP-loss-inducing and the apoptosis-inducing effects of curcumin in SGC-7901 cells were significantly impaired (all P < 0.05). As a result, the proliferation of SGC-7901 cells was maintained by diazoxide treatment.

          Conclusions

          Impaired mitoK ATP opening causes MMP loss, and is involved in curcumin-induced apoptosis in gastric cancer.

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          Most cited references41

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          The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights.

          Traditional Chinese medicine-based herbal medicines have gained increasing acceptance worldwide in recent years and are being pursued by pharmaceutical companies as rich resources for drug discovery. For many years, traditional Chinese medicines (TCM) have been applied for the treatment of cancers in China and beyond. Herbal medicines are generally low in cost, plentiful, and show very little toxicity or side effects in clinical practice. However, despite the vast interest and ever-increasing demand, the absence of strong evidence-based research and the lack of standardization of the herbal products are the main obstacles toward the globalization of TCM. In recent years, TCM research has greatly accelerated with the advancement of analytical technologies and methodologies. This review of TCM specifically used in the treatment of cancer is divided into two parts. Part one provides an overview of the philosophy, approaches and progress in TCM-based cancer therapy. Part two summarizes the current understanding of how TCM-derived compounds function as anticancer drugs. Georg Thieme Verlag KG Stuttgart-New York.
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            Gastric cáncer: Overview

            Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer.
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              Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF).

              It is well known that matrix metalloproteinases (MMPs) act an important role in the invasion, metastasis and angiogenesis of cancer cells. Agents suppressed the MMPs could inhibited the cancer cells migration and invasion. Numerous evidences had shown that curcumin (the active constituent of the dietary spice turmeric) has potential for the prevention and therapy of cancer. Curcumin can inhibit the formation of tumors in animal models of carcinogenesis and act on a variety of molecular targets involved in cancer development. There is however, no available information to address the effects of curcumin on migration and invasion of human lung cancer cells. The anti-tumor invasion and migration effects of lung cancer cells induced by curcumin were examined. Here, we report that curcumin suppressed the migration and invasion of human non-small cell lung cancer cells (A549) in vitro. Our findings suggest that curcumin has anti-metastatic potential by decreasing invasiveness of cancer cells. Moreover, this action was involved in the MEKK3, p-ERK signaling pathways resulting in inhibition of MMP-2 and -9 in human lung cancer A549 cells. Overall, the above data shows that the anticancer effect of curcumin is also exist for the inhibition of migration and invasion in lung cancer cells.
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                Author and article information

                Contributors
                onlyhawk@163.com
                810927700@qq.com
                renhongdoctor@gmail.com
                zhangxiaoyun1981@foxmail.com
                Zhangxu64@163.com
                hxd@lzu.edu.cn
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                19 December 2014
                2014
                : 12
                : 389
                Affiliations
                [ ]Department of General Surgery, second affiliated hospital of Lanzhou University, Lanzhou, Gansu 730000 China
                [ ]The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 China
                [ ]Department of Pathology, Lanzhou University Medical School, 199 West Donggang Road, Lanzhou, Gansu 730000 China
                [ ]Lanzhou University, 199 West Donggang Road, Lanzhou, Gansu 730000 China
                Article
                1914
                10.1186/1477-7819-12-389
                4395964
                25523120
                e002d7f8-9d5a-429a-a66d-34506f609b5e
                © Liu et al.; licensee BioMed Central. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 June 2014
                : 3 December 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Surgery
                apoptosis,curcumin,gastric cancer,katp
                Surgery
                apoptosis, curcumin, gastric cancer, katp

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