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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 620383, 13 pages
http://dx.doi.org/10.1155/2015/620383
Research Article

Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression

1Department of Natural Biotechnology, Nanhua University, Sec. 1, No. 55, Nanhua Road, Dalin, Chiayi 62249, Taiwan
2Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Sec. 4, No. 1650 Taiwan Boulevard, Taichung 40705, Taiwan
3Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Sec. 2, No. 155, Linong Street, Taipei 11221, Taiwan

Received 19 November 2014; Revised 8 January 2015; Accepted 9 January 2015

Academic Editor: Min Li

Copyright © 2015 Yueh-Chiao Yeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Shikonin, a natural naphthoquinone pigment isolated from Lithospermum erythrorhizon, has been reported to suppress growth of various cancer cells. This study was aimed to investigate whether this chemical could also inhibit cell growth of lung cancer cells and, if so, works via what molecular mechanism. To fulfill this, A549 lung cancer cells were treated with shikonin and then subjected to microscopic, biochemical, flow cytometric, and molecular analyses. Compared with the controls, shikonin significantly induced cell apoptosis and reduced proliferation in a dose-dependent manner. Specially, lower concentrations of shikonin (1–2.5 μg/mL) cause viability reduction; apoptosis and cellular senescence induction is associated with upregulated expressions of cell cycle- and apoptotic signaling-regulatory proteins, while higher concentrations (5–10 μg/mL) precipitate both apoptosis and necrosis. Treatment of cells with pifithrin-α, a specific inhibitor of p53, suppressed shikonin-induced apoptosis and premature senescence, suggesting the role of p53 in mediating the actions of shikonin on regulation of lung cancer cell proliferation. These results indicate the potential and dose-related cytotoxic actions of shikonin on A549 lung cancer cells via p53-mediated cell fate pathways and raise shikonin a promising adjuvant chemotherapeutic agent for treatment of lung cancer in clinical practice.