| Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells. | |
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MedLine Citation:
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PMID: 20460760 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Shikonin, a major ingredient in the Chinese traditional herb Lithospermum erythrorhixon, exhibits multiple biological functions including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we delineated the molecular mechanisms of shikonin in the apoptosis of 143B osteosarcoma cells. Shikonin reduced the cell viability of 143B cells in a dose- and time-dependent manner. The IC(50) at 24 h and 48 h for 143B cells was 4.55 and 2.01microM, respectively. A significantly elicited hypodiploid cell population was found in cells treated with 2, 4, and 8microM shikonin for 24 h. Moreover, treatment with shikonin induced reactive oxygen species (ROS) generation, increased extracellular signal-regulated kinase (ERK) phosphorylation, decreased B-cell lymphoma-2 (Bcl2) expression, and was accompanied by poly(ADP-ribose) polymerase (PARP) cleavage. Pretreatment with the antioxidant agent N-acetyl cysteine (NAC) not only reversed shikonin-induced ROS generation but also significantly attenuated the cytotoxic effects of shikonin in 143B cells. Furthermore, NAC attenuated shikonin-induced ERK phosphorylation. Taken together, our results reveal that shikonin increased ROS generation and ERK activation, and reduced Bcl2, which consequently caused the cells to undergo apoptosis. Therefore, shikonin may be a promising chemotherapeutic agent for osteosarcoma treatment. |
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Authors:
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I-Chang Chang; Yu-Jen Huang; Tsay-I Chiang; Chi-Wei Yeh; Li-Sung Hsu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biological & pharmaceutical bulletin Volume: 33 ISSN: 1347-5215 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: Japan |
Other Details:
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Languages: eng Pagination: 816-24 Citation Subset: IM |
Affiliation:
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Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Anti-Inflammatory Agents, Non-Steroidal / pharmacology, therapeutic use Antineoplastic Agents, Phytogenic / pharmacology*, therapeutic use Antioxidants / pharmacology Apoptosis / drug effects* Bone Neoplasms / drug therapy*, metabolism Cell Line, Tumor Dose-Response Relationship, Drug Drugs, Chinese Herbal / pharmacology, therapeutic use Extracellular Signal-Regulated MAP Kinases / metabolism* Humans Inhibitory Concentration 50 Naphthoquinones / pharmacology*, therapeutic use Osteosarcoma / drug therapy*, metabolism Phosphorylation Phytotherapy Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Reactive Oxygen Species / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents, Phytogenic; 0/Antioxidants; 0/Drugs, Chinese Herbal; 0/Naphthoquinones; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 54952-43-1/shikonin; 616-91-1/Acetylcysteine; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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