Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
Regular Article
Shikonin Induces Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase Pathway in Osteosarcoma Cells
I-Chang ChangYu-Jen HuangTsay-I ChiangChi-Wei YehLi-Sung Hsu
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Volume 33 (2010) Issue 5 Pages 816-824

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Abstract

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 IC50 at 24 h and 48 h for 143B cells was 4.55 and 2.01μM, respectively. A significantly elicited hypodiploid cell population was found in cells treated with 2, 4, and 8μM 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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© 2010 The Pharmaceutical Society of Japan
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