Planta Med 2018; 84(09/10): 674-683
DOI: 10.1055/a-0599-1145
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Shikonin Prevents Early Phase Inflammation Associated with Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer and Induces Apoptosis in Human Colon Cancer Cells

Isabel Andújar   *
1   Departament de Farmacologia, Universitat de València, Valencia, Spain
2   FISABIO-Fundación Hospital Universitario Dr. Peset, Valencia, Spain (Present address)
3   Departamento de Ciencias Biomédicas. Universidad Europea de Valencia, Valencia, Spain
,
Alberto Martí-Rodrigo   *
1   Departament de Farmacologia, Universitat de València, Valencia, Spain
,
Rosa María Giner
1   Departament de Farmacologia, Universitat de València, Valencia, Spain
,
José Luis Ríos
1   Departament de Farmacologia, Universitat de València, Valencia, Spain
,
María Carmen Recio
1   Departament de Farmacologia, Universitat de València, Valencia, Spain
› Author Affiliations
Further Information

Publication History

received 27 December 2017
revised 21 March 2018

accepted 26 March 2018

Publication Date:
11 April 2018 (online)

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Abstract

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 shikoninʼs 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.

Key words

Lithospermum erythrorhizon - Boraginaceae - inflammatory bowel disease - shikonin - ulcerative colitis - in vivo

* Isabel Andújar and Alberto Martí-Rodrigo contributed equally to this study.


 

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