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      International Journal of Nanomedicine (submit here)

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      Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

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          Abstract

          Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice.

          Most cited references26

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          Chemopreventive and therapeutic effects of curcumin.

          Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Curcumin is also described as an anti-tumoral, anti-oxidant and anti-inflammatory agent capable of inducing apoptosis in numerous cellular systems. In this review, we describe both properties and mode of action of curcumin on carcinogenesis, gene expression mechanisms and drug metabolism.
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            Curcumin: getting back to the roots.

            The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."
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              Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis.

              Because a role for nuclear factor-kappaB (NF-kappaB) has been implicated in the pathogenesis of pancreatic carcinoma, this transcription factor is a potential target for the treatment of this devastating disease. Curcumin (diferuloylmethane) is a phytochemical with potent NF-kappaB-inhibitory activity. It is pharmacologically safe, but its bioavailability is poor after oral administration. The authors encapsulated curcumin in a liposomal delivery system that would allow intravenous administration. They studied the in vitro and in vivo effects of this compound on proliferation, apoptosis, signaling, and angiogenesis using human pancreatic carcinoma cells. NF-kappaB was constitutively active in all human pancreatic carcinoma cell lines evaluated and liposomal curcumin consistently suppressed NF-kappaB binding (electrophoretic mobility gel shift assay) and decreased the expression of NF-kappaB-regulated gene products, including cyclooxygenase-2 (immunoblots) and interleukin-8 (enzyme-linked immunoassay), both of which have been implicated in tumor growth/invasiveness. These in vitro changes were associated with concentration and time-dependent antiproliferative activity (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin V/propidium iodide staining [fluorescence-activated cell sorting] and polyadenosine-5'-diphosphate-ribose-polymerase cleavage). The activity of liposomal curcumin was equal to or better than that of free curcumin at equimolar concentrations. In vivo, curcumin suppressed pancreatic carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. Liposomal curcumin down-regulated the NF-kappaB machinery, suppressed growth, and induced apoptosis of human pancreatic cells in vitro. Antitumor and antiangiogenesis effects were observed in vivo. The experiments in the current study provide a biologic rationale for treatment of patients suffering from pancreatic carcinoma with this nontoxic phytochemical encapsulated in liposomes for systemic delivery. Copyright 2005 American Cancer Society.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2014
                03 March 2014
                : 9
                : 1139-1152
                Affiliations
                [1 ]Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India
                [2 ]Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (NJIL), Agra, India
                [3 ]Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India
                Author notes
                Correspondence: Mohammad Owais, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India, Tel +91 571 2720 388, Fax +91 571 2721 776, Email owais_lakhnawi@ 123456yahoo.com
                Article
                ijn-9-1139
                10.2147/IJN.S34668
                3945993
                24627632
                9b6e710f-1491-4919-ae7e-3dff87551d49
                © 2014 Farazuddin et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                diferuloylmethane,carcinogenesis,microparticle,nanocells,cancer,curcuma longa
                Molecular medicine
                diferuloylmethane, carcinogenesis, microparticle, nanocells, cancer, curcuma longa

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