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      Xanthorrhizol: a review of its pharmacological activities and anticancer properties

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          Abstract

          Xanthorrhizol (XNT) is a bisabolane-type sesquiterpenoid compound extracted from Curcuma xanthorrhiza Roxb. It has been well established to possess a variety of biological activities such as anticancer, antimicrobial, anti-inflammatory, antioxidant, antihyperglycemic, antihypertensive, antiplatelet, nephroprotective, hepatoprotective, estrogenic and anti-estrogenic effects. Since many synthetic drugs possess toxic side effects and are unable to support the increasing prevalence of disease, there is significant interest in developing natural product as new therapeutics. XNT is a very potent natural bioactive compound that could fulfil the current need for new drug discovery. Despite its importance, a comprehensive review of XNT’s pharmacological activities has not been published in the scientific literature to date. Here, the present review aims to summarize the available information in this area, focus on its anticancer properties and indicate the current status of the research. This helps to facilitate the understanding of XNT’s pharmacological role in drug discovery, thus suggesting areas where further research is required.

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          Most cited references91

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          Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.

          Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
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            Tumor suppressor p53 is a direct transcriptional activator of the human bax gene.

            The bax gene promoter region contains four motifs with homology to consensus p53-binding sites. In cotransfection assays using p53-deficient tumor cell lines, wild-type but not mutant p53 expression plasmids transactivated a reporter gene plasmid that utilized the bax gene promoter to drive transcription of chloramphenicol acetyltransferase. In addition, wild-type p53 transactivated reporter gene constructs containing a heterologous minimal promoter and a 39-bp region from the bax gene promoter in which the p53-binding site consensus sequences reside. Introduction of mutations into the consensus p53-binding site sequences abolished p53 responsiveness of reporter gene plasmids. Wild-type but not mutant p53 protein bound to oligonucleotides corresponding to this region of the bax promoter, based on gel retardation assays. Taken together, the results suggest that bax is a p53 primary-response gene, presumably involved in a p53-regulated pathway for induction of apoptosis.
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              Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.

              The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.
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                Author and article information

                Contributors
                seokfang@live.com
                meenakshii@upm.edu.my
                thiamtsu@zachbio.com
                shamarina@upm.edu.my
                kartinee@upm.edu.my
                shazrul@ukm.edu.my
                yhcheah@zachbio.com
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                21 October 2015
                21 October 2015
                2015
                : 15
                : 100
                Affiliations
                [ ]Department of Biology, Faculty of Science, Universiti Putra Malaysia-UPM, 43400 Serdang, Selangor Malaysia
                [ ]Department of Chemistry, Faculty of Science, Universiti Putra Malaysia-UPM, 43400 Serdang, Selangor Malaysia
                [ ]Department of Biochemistry, Faculty of Science and Technology, Universiti Kebangsaan Malaysia-UKM, 43600 Bangi, Selangor Malaysia
                [ ]ZACH Biotech Depot Sdn. Bhd., 43300 Cheras, Selangor Malaysia
                Article
                255
                10.1186/s12935-015-0255-4
                4618344
                26500452
                e2995552-8ae7-46e3-b942-9ffea4cb7325
                © Oon et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 July 2015
                : 12 October 2015
                Categories
                Review
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy
                xanthorrhizol,curcuma xanthorrhiza roxb.,pharmacological,anticancer
                Oncology & Radiotherapy
                xanthorrhizol, curcuma xanthorrhiza roxb., pharmacological, anticancer

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