Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells
| Autor: | María del Carmen Recio, Rosa M. Giner, José Luis Ríos, Isabel Andújar, Alberto Martí-Rodrigo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Farmacología Anti-Inflammatory Agents Azoxymethane Pharmaceutical Science Caspase 3 Apoptosis Pharmacology Plant Roots Analytical Chemistry Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound In vivo Drug Discovery medicine Animals Humans Colitis Medicine Chinese Traditional Inflammation Mice Inbred BALB C Wound Healing biology Chemistry Lithospermum Organic Chemistry Dextran Sulfate medicine.disease Inflammatory Bowel Diseases Nitric oxide synthase Disease Models Animal 030104 developmental biology Complementary and alternative medicine Caco-2 Colonic Neoplasms biology.protein Molecular Medicine Colitis Ulcerative Female Caco-2 Cells Naphthoquinones |
| Zdroj: | Planta medica. 84(9-10) |
| ISSN: | 1439-0221 |
| Popis: | Shikonin is the main active principle in the root of Lithospermum erythrorhizon, widely used in traditional Chinese medicine for its anti-inflammatory and wound healing properties. Recent research highlights shikonin's antitumor properties and capacity to prevent acute ulcerative colitis. The aim of the present study was to evaluate the ability of shikonin to prevent, in vivo, the early phases of colorectal cancer development, with special focus on its cytotoxic mechanism in vitro. We employed the azoxymethane/dextran sulfate sodium model of colitis in Balb/C mice. Body weight and drinking were monitored throughout the experiment, and length of colon and lesions of the colon were recorded on termination of the experiment in all of the experimental groups. Colons underwent histological evaluation and biochemical analyses [myeloperoxidase activity assay, measurement of interleukin-6, evaluation of proinflammatory enzymes (cyclooxygenase-2 and inducible nitric oxide synthase), and nuclear factor-κB activation by Western blot]. Caco-2 cells were used to evaluate, in vitro, the effect of shikonin on proliferation, cytotoxicity, cell cycle, and apoptosis. Our results reveal that shikonin significantly protected the intestinal tissue of our animals by preventing the shortening of the colorectum and ulcer formation in a dose-dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the production of interleukin-6 and activation of nuclear factor-κB. It induced Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive agent in the azoxymethane/dextran sulfate sodium model through inhibition of the proinflammatory milieu generated during the disease, an important risk factor in cancer development. Ministerio de Ciencia e Innovación (SAF2009-130593-C03-01) Universitat de València (UV-INV-AE13-139455) 2.746 JCR (2018) Q1, 56/228 Plant Sciences, 5/27 Integrative & Complementary Medicine; Q2, 29/61 Chemistry, Medicinal, 121/267 Pharmacology & Pharmacy 0.559 SJR (2018) Q1, 21/109 Complementary and Alternative Medicine; Q2, 50/125 Analytical Chemistry, 79/170 Drug Discovery, 66/218 Pharmaceutical Science, 88/185 Organic Chemistry; Q3, 172/335 Pharmacology, 120/177 Molecular Medicine No data IDR 2018 UEV |
| Databáze: | OpenAIRE |
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