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      The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

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          Abstract

          Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.

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          Most cited references 61

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          Proliferating cell nuclear antigen (PCNA): a dancer with many partners.

          Proliferating cell nuclear antigen (PCNA) was originally characterised as a DNA sliding clamp for replicative DNA polymerases and as an essential component of the eukaryotic chromosomal DNA replisome. Subsequent studies, however, have revealed its striking ability to interact with multiple partners, which are involved in several metabolic pathways, including Okazaki fragment processing, DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling and cell cycle regulation. PCNA in mammalian cells thus appears to play a key role in controlling several reactions through the coordination and organisation of different partners. Two major questions have emerged: how do these proteins access PCNA in a coordinated manner, and how does PCNA temporally and spatially organise their functions? Structural and biochemical studies are starting to provide a first glimpse of how both tasks can be achieved.
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            Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings.

            In the present study a methodological approach is taken which quantitates aberrant dysplastic crypts in the unsectioned murine colon. C57BL/6J or CF1 female mice (7-8 weeks old) were injected (i.p.) with azoxymethane (5 mg/kg body wt./week) for 4 weeks. Their colons were excised, cut open on the median axis and fixed flat in buffered formalin. Unsectioned colons were stained with methylene blue. The mucosal side was examined under a light microscope. The aberrant crypts, which are larger and have a thicker epithelial lining, were easily visualized using X 4 or X 10 objectives. CF1 mice, which are more sensitive to developing colon tumors, had a higher number of aberrant crypts/colon than their less sensitive counterparts, C57BL/6J mice (5.0 +/- 0.7 vs. 2.4 +/- 0.7). The usefulness of this observation as a possible measure of neoplastic events is discussed in the animal and human situation.
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              The genetics of hereditary colon cancer.

               Anil K Rustgi (2007)
              The genetic basis of sporadic colorectal cancer has illuminated our knowledge of human cancer genetics. This has been facilitated and catalyzed by an appreciation and deep understanding of the forms of colorectal cancer that harbor an inherited predisposition, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, the hamartomatous polyposis syndromes, and certain other rare syndromes. Identification of germline mutations in pivotal genes underlying the inherited forms of colorectal cancer has yielded many dividends, including functional dissection of critical molecular pathways that have been revealed to be important in development, cellular homeostasis, and cancer; new approaches in chemoprevention, molecular diagnostics and genetic testing, and therapy; and underscoring genotypic-phenotypic relationships.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                27 July 2015
                : 9
                : 3911-3922
                Affiliations
                [1 ]Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [2 ]Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
                [3 ]Department of Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia
                [4 ]Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                [5 ]Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia
                Author notes
                Correspondence: Elham Rouhollahi, Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Jalan Pantai Lembah, Kuala Lumpur 50603, Malaysia, Tel +60 3 7967 5725, Fax +60 3 7967 4791, Email elhamrouhollahi@ 123456gmail.com
                Article
                dddt-9-3911
                10.2147/DDDT.S84560
                4524378
                © 2015 Rouhollahi 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.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                colon cancer, pcna, zingiberaceae

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