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      Tanshinone IIA inhibits glucose metabolism leading to apoptosis in cervical cancer

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          Abstract

          Cancer requires aerobic glycolysis to supply the energy required for proliferation. Existing evidence has revealed that blocking glycolysis results in apoptosis of cancer cells. Tanshinone IIA (Tan IIA) is a diterpenoid naphthoquinone found in traditional Chinese medicine, Danshen ( Salvia sp.). Tan IIA exhibits potential anticancer activity. However, its effect on cell viability of human cervical cancer cells and its mechanism are unknown. The aim of the present study was to determine the effect of Tan IIA on proliferation and glucose metabolism in cervical cancer cells. Cell viability was measured by MTT assay, apoptosis was determined using flow cytometry and glucose uptake, lactate production, and adenosine triphosphate content were measured to assess glucose metabolism. The expression of apoptosis-associated proteins was detected by western blotting and the antitumor activity of Tan IIA in vivo was evaluated in cervical carcinoma-bearing mice. The results revealed Tan IIA treatment resulted in a considerable reduction in the viability of SiHa cells. Tan IIA decreased the expression of HPV oncogenes E6 and E7, induced apoptosis and also decreased glycolysis by suppressing the activity of the intracellular AKT/mTOR and HIF-1α. In vivo, treatment with Tan IIA resulted in a 72.7% reduction in tumor volume. The present study highlights the potential therapeutic value of Tan IIA, which functions by inducing apoptosis and may be associated with inhibition of glycolysis.

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          Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin

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            Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction

            Aerobic glycolysis regulates T cell function. However, if and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity remains a question in cancer patients. Here we report that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNA101 and microRNA26a, which constrained expression of the methyltransferase EZH2. EZH2 activated the Notch pathway by suppressing Notch repressors, Numb and Fbxw7, via H3K27me3, and consequently stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling. Moreover, human shRNA-knockdown-EZH2-deficient T cells elicited poor anti-tumor immunity. EZH2+CD8+ T cells were associated with improved cancer patient survival. Together, the data unveil a novel metabolic target and mechanism of cancer immune evasion.
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              Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

              The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                November 2019
                27 August 2019
                27 August 2019
                : 42
                : 5
                : 1893-1903
                Affiliations
                [1 ]Faculty of Medicine, Beihua University, Jilin, Jilin 132013, P.R. China
                [2 ]Department of Biochemistry, Jilin Medical University, Jilin, Jilin 132013, P.R. China
                Author notes
                Correspondence to: Dr Ruowen Zhang, Faculty of Medicine, Beihua University, 3999 Binjiang East Road, Jilin, Jilin 132013, P.R. China, E-mail: zrw1828@ 123456163.com
                Dr Wei Zhang, Department of Biochemistry, Jilin Medical University, 5 Jilin Street, Jilin, Jilin 132013, P.R. China, E-mail: jlmpczw@ 123456163.com
                [*]

                Contributed equally

                Article
                OR-0-0-7294
                10.3892/or.2019.7294
                6775814
                31485631
                9222b9d3-f6af-4714-980e-e278de26c823
                Copyright: © Liu et al.

                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
                : 13 February 2019
                : 16 July 2019
                Categories
                Articles

                tanshinone iia,glycolysis,apoptosis,cervical cancer
                tanshinone iia, glycolysis, apoptosis, cervical cancer

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