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      Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis

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      , , ,
      Oncology Reports
      D.A. Spandidos
      berberine, osteosarcoma, caspase-1, IL-1β

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          Abstract

          Osteosarcoma is one of the most devastating cancers with associated poor prognosis. Chronic bone inflammation frequently predisposes to tumorigenesis and progression of osteosarcoma. In the tumor inflammatory microenvironment, caspase-1 and its processed cytokines such as interleukin 1β (IL-1β) play an important role in the occurrence and development of cancer. Berberine is an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, which has been found to exhibit significant anticancer effects on a wide spectrum of carcinomas including osteosarcoma. However, the mechanisms underlying the anticancer effects of berberine in osteosarcoma remain poorly understood and their elucidation is critical for developing improved therapies. In the present study, we investigated the potential mechanism underlying the anticancer effect of berberine in osteosarcoma. We found that the expression of caspase-1 and its downstream target IL-1β were higher in osteosarcoma cells compared with normal cells both in vitro and in vivo. Furthermore, administration of berberine is capable of reducing the expression of caspase-1 and IL-1β in osteosarcoma cells and inhibiting the growth of tumor cells. Based on the above, for the first time, we propose the hyposis that berberine could gengerate an anti-osteosarcoma property through downregulating caspase-1/IL-1β inflammatory signaling axis.

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          Most cited references23

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          Converging roles of caspases in inflammasome activation, cell death and innate immunity.

          Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes that direct inflammasome and interferon responses to fine-tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.
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            Inflammation and necrosis promote tumour growth.

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              Molecular cloning of the interleukin-1 beta converting enzyme.

              Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor. A complementary DNA encoding a protease that carries out this cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells to process precursor IL-1 beta to the mature form. Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                January 2017
                16 December 2016
                16 December 2016
                : 37
                : 2
                : 729-736
                Affiliations
                Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
                Author notes
                Correspondence to: Dr Wenbo Wang, Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Road, Harbin, Heilongjiang 150001, P.R. China, E-mail: 280798492@ 123456qq.com
                Article
                or-37-02-0729
                10.3892/or.2016.5327
                5355653
                28000894
                ac10156a-7a11-4c05-9775-3e3347808f52
                Copyright: © Jin 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
                : 19 July 2016
                : 07 December 2016
                Categories
                Articles

                berberine,osteosarcoma,caspase-1,il-1β
                berberine, osteosarcoma, caspase-1, il-1β

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