The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2ARE Pathway
Joint Authors
Wang, Zhenhua
Zheng, Qiusheng
Zhang, Bo
Chen, Hongmei
Chen, Na
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-10-15
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
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 redox homeostasis changes towards oxidation are necessary to support Shikonin-induced differentiation, which was proven by additional enzymatic and non-enzymatic redox modulators.
A statistically significant and dose-dependent increase (P<0.05) was recorded with regard to the unique expression levels of the Nrf2/ARE downstream target genes in HL-60 cells undergoing late differentiation, which were restored with further antioxidants employed with the Shikonin treatment.
Our research demonstrated that Shikonin is a differentiation-inducing agent, and its mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox homeostasis, thus facilitating differentiation.
American Psychological Association (APA)
Zhang, Bo& Chen, Na& Chen, Hongmei& Wang, Zhenhua& Zheng, Qiusheng. 2012. The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2ARE Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-497513
Modern Language Association (MLA)
Zhang, Bo…[et al.]. The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2ARE Pathway. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-497513
American Medical Association (AMA)
Zhang, Bo& Chen, Na& Chen, Hongmei& Wang, Zhenhua& Zheng, Qiusheng. The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2ARE Pathway. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-497513
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-497513