19
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Resveratrol, a natural polyphenolic phytoalexin, has potent anti-tumor activity. Recently, it was found to induce autophagy in cancer cells. However, the effects of resveratrol on autophagy in non-small-cell lung cancer (NSCLC) cells have not yet been clearly elucidated.

          Materials and methods

          A549 and H1299 cells were treated with different concentrations of resveratrol. Cell growth and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. A549 cells were then treated with 200 μM resveratrol or SRT1720. Cell autophagy was detected by western blot and immunofluorescence.

          Results

          In this study, we found that resveratrol exerted the anti-tumor effect through inhibiting cell proliferation and promoting cell apoptosis in NSCLC cells dose-dependently. Resveratrol has also increased the relative expression of Beclin1 and LC3 II/I while decreased p62 expression, suggesting that resveratrol induced autophagy in NSCLC cells. In addition, resveratrol increased SIRT1 expression and SIRT1 activator SRT1720-induced autophagy of NSCLC cells. SIRT1 knockdown reduced resveratrol-induced autophagy significantly. These results indicated that resveratrol might induce autophagy through upregulating SIRT1 expression. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine or SIRT1 inhibitor nicotinamide significantly suppressed proliferation while promoted apoptosis compared with the resveratrol 200 μM group, suggesting that resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival and inhibiting autophagy can enhance the anti-tumor effect of resveratrol. Besides that, resveratrol treatment inhibited Akt/mTOR while p38-MAPK was activated in NSCLC cells in a dose-dependent manner. Activating Akt/ mTOR pathway by IGF-1 or inhibiting p-38-MAPK pathway by doramapimod significantly inhibited cell proliferation while increased cell apoptosis of NSCLC cells compared with the resveratrol 200 μM group.

          Conclusion

          Taken together, our findings suggest that resveratrol inhibited proliferation but induced apoptosis and autophagy via inhibiting Akt/mTOR and activating p38-MAPK pathway. Resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival. Therefore, inhibition of autophagy may enhance the anti-tumor activity of resveratrol in NSCLC.

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer statistics for Hispanics/Latinos, 2012.

          Hispanics/Latinos are the largest and fastest growing major demographic group in the United States, accounting for 16.3% (50.5 million/310 million) of the US population in 2010. In this article, the American Cancer Society updates a previous report on cancer statistics for Hispanics using incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. In 2012, an estimated 112,800 new cases of cancer will be diagnosed and 33,200 cancer deaths will occur among Hispanics. In 2009, the most recent year for which actual data are available, cancer surpassed heart disease as the leading cause of death among Hispanics. Among US Hispanics during the past 10 years of available data (2000-2009), cancer incidence rates declined by 1.7% per year among men and 0.3% per year among women, while cancer death rates declined by 2.3% per year in men and 1.4% per year in women. Hispanics have lower incidence and death rates than non-Hispanic whites for all cancers combined and for the 4 most common cancers (breast, prostate, lung and bronchus, and colorectum). However, Hispanics have higher incidence and mortality rates for cancers of the stomach, liver, uterine cervix, and gallbladder, reflecting greater exposure to cancer-causing infectious agents, lower rates of screening for cervical cancer, differences in lifestyle and dietary patterns, and possibly genetic factors. Strategies for reducing cancer risk among Hispanics include increasing utilization of screening and available vaccines, as well as implementing effective interventions to reduce obesity, alcohol consumption, and tobacco use. Copyright © 2012 American Cancer Society, Inc.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            SIRT1 controls endothelial angiogenic functions during vascular growth.

            The nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase Sir2 regulates life-span in various species. Mammalian homologs of Sir2 are called sirtuins (SIRT1-SIRT7). In an effort to define the role of sirtuins in vascular homeostasis, we found that among the SIRT family, SIRT1 uniquely regulates angiogenesis signaling. We show that SIRT1 is highly expressed in the vasculature during blood vessel growth, where it controls the angiogenic activity of endothelial cells. Loss of SIRT1 function blocks sprouting angiogenesis and branching morphogenesis of endothelial cells with consequent down-regulation of genes involved in blood vessel development and vascular remodeling. Disruption of SIRT1 gene expression in zebrafish and mice results in defective blood vessel formation and blunts ischemia-induced neovascularization. Through gain- and loss-of-function approaches, we show that SIRT1 associates with and deacetylates the forkhead transcription factor Foxo1, an essential negative regulator of blood vessel development to restrain its anti-angiogenic activity. These findings uncover a novel and unexpected role for SIRT1 as a critical modulator of endothelial gene expression governing postnatal vascular growth.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The autophagy effector Beclin 1: a novel BH3-only protein.

              BH3 domains were originally discovered in the context of apoptosis regulators and they mediate binding of proapoptotic Bcl-2 family members to antiapoptotic Bcl-2 family members. Yet, recent studies indicate that BH3 domains do not function uniquely in apoptosis regulation; they also function in the regulation of another critical pathway involved in cellular and tissue homeostasis called autophagy. Antiapoptotic Bcl-2 homologs downregulate autophagy through interactions with the essential autophagy effector and haploinsufficient tumor suppressor, Beclin 1. Beclin 1 contains a BH3 domain, similar to that of Bcl-2 proteins, which is necessary and sufficient for binding to antiapoptotic Bcl-2 homologs and required for Bcl-2-mediated inhibition of autophagy. This review will summarize the evidence that the BH3 domain of Beclin 1 serves as a key structural motif that enables Bcl-2 to function not only as an antiapoptotic protein, but also as an antiautophagy protein.
                Bookmark

                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                02 November 2018
                : 11
                : 7777-7786
                Affiliations
                [1 ]Department of Respiration, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
                [2 ]Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
                [3 ]Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China, lilishandongjn@ 123456163.com
                Author notes
                Correspondence: Li Li, Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 324# Jingwu Road, Jinan 250021, Shandong, China, Tel +86 531 5867 5120, Email lilishandongjn@ 123456163.com
                Article
                ott-11-7777
                10.2147/OTT.S159095
                6223384
                30464525
                20ee0369-75f6-416a-8584-08173c97970c
                © 2018 Wang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                resveratrol,sirt1,autophagy,non-small-cell lung cancer
                Oncology & Radiotherapy
                resveratrol, sirt1, autophagy, non-small-cell lung cancer

                Comments

                Comment on this article