1. β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo.
- Author
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Zhen-Jun S, Yuan-Yuan Z, Ying-Ying F, Shao-Ju J, Jiao Y, Xiao-Wei Z, Jian C, Yao X, and Li-Ming Z
- Subjects
- Animals, Antineoplastic Agents, Phytogenic therapeutic use, Apoptosis drug effects, Cell Line, Tumor drug effects, Cell Proliferation drug effects, Down-Regulation, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal therapeutic use, Female, G1 Phase drug effects, Humans, Mice, Mice, Inbred BALB C, Naphthoquinones therapeutic use, Receptor, Notch1 antagonists & inhibitors, Resting Phase, Cell Cycle drug effects, Signal Transduction, Transplantation, Heterologous, Antineoplastic Agents, Phytogenic pharmacology, Naphthoquinones pharmacology, Receptor, Notch1 physiology, Stomach Neoplasms drug therapy
- Abstract
β,β-Dimethylacrylshikonin (DA) is a major component of Radix Lithospermum erythrorhizon and has various biological activities. We have investigated the inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in vivo. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis. Hence, perturbed Notch signaling may contribute to tumorigenesis. In the present study, we evaluated whether DA could be an effective inhibitor on cell growth in human gastric cancer cell line, and also the molecular mechanisms. Using multiple cellular and molecular approaches such as MTT assay, colony formation assay, DAPI staining, flow cytometry, real-time PCR and Western blot analysis, we found that DA inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis revealed the involvement of cell cycle regulated proteins in DA-mediated of G₀-G₁ arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and in vivo. Our data demonstrated that DA is a potent inhibitor of progression of gastric cancer cells, which could be due to attenuation of Notch-1. We also suggest that DA could be further developed as a potential therapeutic agent for the treatment of gastric cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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