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      Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

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          Abstract

          Artesunate (ART) is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Animals were divided into four groups ( n = 6): Group I - vehicle (1 mM ethylenediaminetetraacetic acid), Group II - DMH (20 mg/kg), Group III - DMH + 5-fluorouracil (81 mg/kg), Group IV - DMH + ART (6.7 mg/kg). After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO), antioxidant status, average number of aberrant crypt foci (ACF), and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

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          Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings.

          R P Bird (1987)
          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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            Colorectal carcinogenesis: Review of human and experimental animal studies

            Takuji Tanaka (2009)
            This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model) will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma). These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.
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              Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate.

              R Dell'eva, L Anfosso, Ulrich Pfeffer … (2004)
              Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Adv Pharm Technol Res
                Journal ID (iso-abbrev): J Adv Pharm Technol Res
                Journal ID (publisher-id): JAPTR
                Title: Journal of Advanced Pharmaceutical Technology & Research
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2231-4040
                ISSN (Electronic): 0976-2094
                Publication date (Print): Jul-Sep 2017
                Volume: 8
                Issue: 3
                Pages: 102-107
                Affiliations
                [1]Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [1 ]Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                [2 ]Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
                Author notes
                Address for correspondence: Dr. Sazal Patyar, Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. E-mail: sazalpatyar@ 123456yahoo.co.in
                Article
                Publisher ID: JAPTR-8-102
                DOI: 10.4103/japtr.JAPTR_61_17
                PMC ID: 5527695
                SO-VID: bd425999-075c-4495-b76a-623a9382d4bb
                Copyright © Copyright: © 2017 Journal of Advanced Pharmaceutical Technology & Research
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Subject: Original Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: aberrant crypt foci,artemisinin,artesunate,apoptosis,cytokines,oxidative stress,tumor necrosis factor-α
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: aberrant crypt foci, artemisinin, artesunate, apoptosis, cytokines, oxidative stress, tumor necrosis factor-α

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