the critical role of redox homeostasis in shikonin-induced hl-60 cell differentiation via unique modulation of the nrf2are pathway氧化还原内稳态的关键作用shikonin-induced hl-60通过独特的调制nrf2are通路细胞分化.pdfVIP

Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2012, Article ID 781516, 12 pages doi:10.1155/2012/781516 Research Article The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway Bo Zhang,1 Na Chen,1 Hongmei Chen,1 Zhenhua Wang,1 and Qiusheng Zheng1, 2 1 Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China 2 Life Sciences School, Yantai University, Yantai 264005, China Correspondence should be addressed to Qiusheng Zheng, zqsyt@ Received 18 August 2012; Accepted 11 September 2012 Academic Editor: Pranela Rameshwar Copyright © 2012 Bo Zhang 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. Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive to Shikonin, with evidence showing both the prooxidative activities and proapoptotic effects of micromolar concentrations of Shikonin. However, the mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the prodifferentiated profiles of Shikonin and evaluated the redox homeostasis during HL-60 differentiation. The data showed a strong dose-response relationship between Shikonin exposure and the characteristics of HL-60 differentiation in terms of morphology changes, nitroblue tetrazolium (NBT) reductive activity, and the expression level of surface antigens CD11b/CD14. During drug exposure, intercellular red