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      Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer

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          Abstract

          Traditional medicine and diet has served mankind through the ages for prevention and treatment of most chronic diseases. Mounting evidence suggests that chronic inflammation mediates most chronic diseases, including cancer. More than other transcription factors, nuclear factor-kappaB (NF-κB) and STAT3 have emerged as major regulators of inflammation, cellular transformation, and tumor cell survival, proliferation, invasion, angiogenesis, and metastasis. Thus, agents that can inhibit NF-κB and STAT3 activation pathways have the potential to both prevent and treat cancer. In this review, we examine the potential of one group of compounds called triterpenes, derived from traditional medicine and diet for their ability to suppress inflammatory pathways linked to tumorigenesis. These triterpenes include avicins, betulinic acid, boswellic acid, celastrol, diosgenin, madecassic acid, maslinic acid, momordin, saikosaponins, platycodon, pristimerin, ursolic acid, and withanolide. This review thus supports the famous adage of Hippocrates, “Let food be thy medicine and medicine be thy food”.

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          Points of control in inflammation.

          Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.
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            NF-kappaB in cancer: from innocent bystander to major culprit.

            Nuclear factor of kappaB (NF-kappaB) is a sequence-specific transcription factor that is known to be involved in the inflammatory and innate immune responses. Although the importance of NF-KB in immunity is undisputed, recent evidence indicates that NF-kappaB and the signalling pathways that are involved in its activation are also important for tumour development. NF-kappaB should therefore receive as much attention from cancer researchers as it has already from immunologists.
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              Drug discovery from medicinal plants.

              Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.
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                Author and article information

                Journal
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                22 October 2010
                October 2010
                : 2
                : 10
                : 2428-2466
                Affiliations
                Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston 77030, TX, USA; Email: vryadav@ 123456mdanderson.org (V.R.Y.)
                Author notes
                [* ] Author to whom correspondence should be addressed; Email: aggarwal@ 123456mdanderson.org ; Tel.: +1 713 794 1817; Fax: +1 713 606 3399.
                Article
                toxins-02-02428
                10.3390/toxins2102428
                3153165
                22069560
                90294928-0d87-4b77-86b5-0b48b38b413a
                © 2010 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 license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 30 August 2010
                : 23 September 2010
                : 15 October 2010
                Categories
                Review

                Molecular medicine
                triterpenoids,nuclear factor-κb,inflammation,tumor cell proliferation,invasion,angiogenesis,apoptosis

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