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      Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis

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          Abstract

          A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted from Arachniodes exilis (TFAE) in vivo. Several biochemical assays including hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted from Arachniodes exilis (TFAE). The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1 α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

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          Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.

          H Zhong, A M De Marzo, E Laughner … (1999)
          Neovascularization and increased glycolysis, two universal characteristics of solid tumors, represent adaptations to a hypoxic microenvironment that are correlated with tumor invasion, metastasis, and lethality. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. HIF-1 transcriptional activity is determined by regulated expression of the HIF-1alpha subunit. In this study, HIF-1alpha expression was analyzed by immunohistochemistry in 179 tumor specimens. HIF-1alpha was overexpressed in 13 of 19 tumor types compared with the respective normal tissues, including colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate, and renal carcinomas. HIF-1alpha expression was correlated with aberrant p53 accumulation and cell proliferation. Preneoplastic lesions in breast, colon, and prostate overexpressed HIF-1alpha, whereas benign tumors in breast and uterus did not. HIF-1alpha overexpression was detected in only 29% of primary breast cancers but in 69% of breast cancer metastases. In brain tumors, HIF-1alpha immunohistochemistry demarcated areas of angiogenesis. These results provide the first clinical data indicating that HIF-1alpha may play an important role in human cancer progression.
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            HIF-1: mediator of physiological and pathophysiological responses to hypoxia.

            Gregg L. Semenza (2000)
            All organisms can sense O(2) concentration and respond to hypoxia with adaptive changes in gene expression. The large body size of mammals necessitates the development of multiple complex physiological systems to ensure adequate O(2) delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O(2) homeostasis. HIF-1 is required for the establishment of key physiological systems during development and their subsequent utilization in fetal and postnatal life. HIF-1 also appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies. Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders.
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              Focus on hepatocellular carcinoma.

              Jordi Bruix, Loreto Boix, Harm A. G. M. Sala … (2004)
              Article 0 comments Cited 128 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Huimin Li:
                ORCID: http://orcid.org/0000-0003-0773-1511
                Dengzhao Jiang:
                ORCID: http://orcid.org/0000-0002-0288-1476
                Journal
                Journal ID (nlm-ta): Evid Based Complement Alternat Med
                Journal ID (iso-abbrev): Evid Based Complement Alternat Med
                Journal ID (publisher-id): ECAM
                Title: Evidence-based Complementary and Alternative Medicine : eCAM
                Publisher: Hindawi
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date (Print): 2017
                Publication date (Electronic): 19 November 2017
                Volume: 2017
                Electronic Location Identifier: 5310563
                Affiliations
                1School of Basic Medical Science, Jiujiang University, No. 320 Xunyang Eastern Road, Jiujiang, Jiangxi 332000, China
                2Key Laboratory of System Biomedicine of Jiangxi Province, Jiujiang, Jiangxi 332000, China
                3School of Pharmacy and Life Sciences, Jiujiang University, No. 320 Xunyang Eastern Road, Jiujiang, Jiangxi 332000, China
                Author notes

                Academic Editor: Célia Cabral

                Author information
                http://orcid.org/0000-0003-0773-1511
                http://orcid.org/0000-0002-0288-1476
                Article
                DOI: 10.1155/2017/5310563
                PMC ID: 5733995
                SO-VID: c633d8e6-b096-4fbc-b8a9-3c7451780f38
                Copyright © Copyright © 2017 Huimin Li et al.
                License:

                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
                Date received : 9 August 2017
                Date revision received : 9 October 2017
                Date accepted : 29 October 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: NSFC81560642
                Funded by: Natural Science Foundation of Jiangxi Province
                Award ID: 20142BAB205081
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Complementary & Alternative medicine
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine

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