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      The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer


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          Glioblastoma multiforme (GBM) is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP), are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB). Taken together, its actions have been shown to have anti-proliferative, anti-chemoresistance, anti-invasion, anti-migration, and anti-dissemination effects against GBM. In addition, a local drug delivery system for the subcutaneous and intracranial implantation of BP wafers that significantly reduce tumor size in xenograft models, as well as orthotopic and spontaneous brain tumors in animal models, has been developed. Isochaihulactone (ICL), another kind of plant product, possesses a broad spectrum of pharmacological activities, including impacts on cancer cell apoptosis and cell cycle arrest, as well as anti-proliferative and anti-chemoresistance effects. Furthermore, these actions have been specifically shown to have cancer-fighting effects on GBM. In short, the results of various studies reviewed herein have provided substantial evidence indicating that BP and ICH are promising novel anticancer compounds with good potential for clinical applications.

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          Most cited references69

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          CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009.

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            Caspases: intracellular signaling by proteolysis.

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              Caspases: killer proteases

              Caspases (cysteinyl aspartate-specific proteinases) mediate highly specific proteolytic cleavage events in dying cells, which collectively manifest the apoptotic phenotype. The key and central role that these enzymes play in a biochemical cell-suicide pathway has been conserved throughout the evolution of multicellular eukaryotes.

                Author and article information

                Int J Mol Sci
                Int J Mol Sci
                International Journal of Molecular Sciences
                30 January 2018
                February 2018
                : 19
                : 2
                [1 ]Department of Pediatrics, Tung’s Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan; fanhuengchuen@ 123456yahoo.com.tw (H.-C.F.); chi-cs@ 123456hotmail.com (C.-S.C.)
                [2 ]Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan; yogurt8306@ 123456gmail.com
                [3 ]Department of Medical Research, Tung’s Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan
                [4 ]Department of Surgery, Tung’s Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan; tungminche@ 123456yahoo.com.tw
                [5 ]Buddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien 970, Taiwan; shinnzong@ 123456yahoo.com.tw
                [6 ]Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
                [7 ]Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
                Author notes
                [* ]Correspondence: arthewduke@ 123456gmail.com ; Tel.: +886-3-856-1825 (ext. 15615)
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 07 January 2018
                : 25 January 2018

                Molecular biology
                blood-brain barrier (bbb),n-butylidenephthalide (bp),glioblastoma multiforme (gbm),isochaihulactone (icl),o-6-methylguanine-dna methyltransferase (mgmt),protein kinase c (pkc),retinoblastoma protein (rb),temozolomide (tmz)


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