期刊
PHYTOTHERAPY RESEARCH
卷 26, 期 12, 页码 1927-1933出版社
WILEY-BLACKWELL
DOI: 10.1002/ptr.4673
关键词
FOXO3; pachastrissamine (PA); apoptosis; ERK; melanoma; phytosphingosine
资金
- Rural Development Administration, Republic of Korea [200905FHT010102004]
Melanoma cells are relatively resistant to apoptosis compared with other tumor cell types, and thus, chemotherapy, radiotherapy and immunotherapy are not effective in treating melanoma. Pachastrissamine (PA) exhibits cytotoxic activity and promotes apoptosis in several cancer cells. However, its specific molecular mechanisms have not been characterized fully. This study investigated the antimelanoma effect of PA, an anhydrophytosphingosine derived from marine sponge, and its underlying molecular mechanisms. The data demonstrated that treatment with PA inhibited the phosphorylation of ERK and subsequent ERK-mediated FOXO3 phosphorylation in melanoma cells. Interestingly, PA did not inhibit AKT-mediated FOXO3 phosphorylation. Therefore, it appears that PA-induced apoptosis results from the inhibition of ERK. Furthermore, intravenous administration of PA was found to suppress melanoma cell growth in a C57BL6 mouse without causing side effects. Additionally, PA inhibited the production of Cdk2, which is involved in cell cycle regulation. Taken together, inhibition of melanoma cell growth by PA is a result of the inhibition of ERK-mediated FOXO3 downregulation and decreased Cdk2 levels. The results of this study imply that dual inhibition of the ERK pathway and cell cycle progression could be an effective approach to control the growth of melanoma cells. Copyright (c) 2012 John Wiley & Sons, Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据