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      Chemical Composition and Antiproliferative Effects of a Methanol Extract of Aspongopus chinensis Dallas

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          Abstract

          Natural products from insects can be potent sources for developing a variety of pharmaceutical products. Aspongopus chinensis Dallas has been used as a traditional Chinese medicine and there are several clinical evidences to support its anticancer activity. However, the anticancer active ingredients present in A. chinensis remain unidentified. In the present study, we investigated the anticancer effects of a methanol extract of A. chinensis (AME). Gas chromatography mass spectrometry was used to analyse the chemical composition of AME. The cell viability of MDA-MB-453 and HCC-1937 cells treated with different concentrations of AME was detected by MTT assay and the ratio of cells in different cell cycle phases was analysed by flow cytometry. The expression of genes associated with cell cycle was analysed by real-time PCR assay. The results showed that oleic acid (25.39%) and palmitic acid (21.798%) are the main anticancer compounds present in AME. There was a concentration-dependent decrease in the proliferation of MDA-MB-453 and HCC-1937 cells. Moreover, treatment with AME induced a S-phase arrest in the cells. Real-time PCR assay demonstrated that AME could significantly downregulate the expression of CDC20, AURKB, PLK1, CCNB2, and TOP2A mRNAs and upregulate the expression of GADD45A mRNA. We demonstrate that the methanol extract of A. chinensis could be a potential natural alternative or complementary therapy for breast cancer.

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          Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.

          Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.
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            Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy

            Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on volasertib (BI 6727; an investigational agent), a potent and selective Plk inhibitor. Volasertib has shown promising activity in various cancer cell lines and xenograft models of human cancer. Trials performed to date suggest that volasertib has clinical efficacy in a range of malignancies, with the most promising results seen in patients with acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that volasertib combined with low-dose cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile, volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biologic rationale for Plk1 inhibitors in cancer, the clinical development of volasertib to date in solid tumors and AML, and the future identification of biomarkers that might predict response to volasertib and help determine the role of this agent in the clinic.
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              Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage.

              DNA damage causes stabilization of p53, leading to G1 arrest through induction of p21cip1. As this process requires transcription, several hours are needed to exert this response. We show that DNA damage causes an immediate and p53-independent G1 arrest, caused by rapid proteolysis of cyclin D1. Degradation is mediated through a previously unrecognized destruction box in cyclin D1 and leads to a release of p21cip1 from CDK4 to inhibit CDK2. Interference with cyclin D1 degradation prevents initiation of G1 arrest and renders cells more susceptible to DNA damage, indicating that cyclin D1 degradation is an essential component of the cellular response to genotoxic stress. Thus, induction of G1 arrest in response to DNA damage is minimally a two step process: a fast p53-independent initiation of G1 arrest mediated by cyclin D1 proteolysis and a slower maintenance of arrest resulting from increased p53 stability.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2019
                30 May 2019
                30 May 2019
                : 2019
                : 2607086
                Affiliations
                1Provincial Key Laboratory for Agricultural Pest Management of Mountainous Region, Institute of Entomology, Guizhou University, Guiyang, Guizhou 550025, China
                2Department of Histology and Embryology, Zunyi Medical University, Zunyi, Guizhou 563000, China
                3College of Life Science, Guizhou University, Guiyang, Guizhou 550025, China
                Author notes

                Guest Editor: Yong-Ung Kim

                Author information
                http://orcid.org/0000-0001-6715-2963
                http://orcid.org/0000-0002-0523-6704
                Article
                10.1155/2019/2607086
                6582901
                5deda02f-af35-42ab-afaa-f1785ee75796
                Copyright © 2019 Jun Tan et al.

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

                History
                : 12 March 2019
                : 9 May 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81803968
                Award ID: 81360612
                Funded by: Special Funds for Excellent Young Scientific Talent in Guizhou
                Award ID: [2015]25
                Funded by: Master's Start-Up Foundation of Zunyi Medical University
                Award ID: F-672
                Funded by: Graduate Education Innovation Project of Guizhou Province
                Award ID: (2018)044
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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