Department of Dermatology, Competence Center skintegral, University Medical Center Freiburg, Germany.
J Invest Dermatol. 2010 Jan;130(1):113-23. doi: 10.1038/jid.2009.248.
It has been shown recently that triterpenes inhibit cancer cell growth of various cell types in vitro. In this work, the effect of highly purified triterpenes (TE) with betulin as the major compound (>80% w/w) on cell proliferation, apoptosis, and differentiation of human keratinocytes was analyzed in vitro, ex vivo, and in vivo. In vitro, TE increased calcium influx into primary keratinocytes and upregulated various differentiation markers including keratin 10. TE also specifically increased the expression of the non-selective transient receptor potential canonical (subtype) 6 (TRPC6) in keratinocytes, and knocking down TRPC6 inhibited keratin 10 upregulation. Ex vivo, in human skin explants TE induced the expression of TRPC6 in the epidermis and increased DNA fragmentation of terminally differentiating keratinocytes. Topical treatment with TE of actinic keratoses, that represent in situ squamous cell carcinomas with disturbed epithelial differentiation, resulted in downgrading of aberrant Ki67 expression and upregulation of keratin 10 in vivo. Our data indicate that TE promotes keratinocyte differentiation in vitro and in vivo. This effect seems to be mediated at least in part by TRPC6.
最近已经证明，三萜类化合物在体外抑制各种细胞类型的癌细胞生长。在这项工作中，分析了具有较高纯度的三萜类化合物（TE）（主要化合物为桦木醇>80%w/w）对人角质形成细胞体外、离体和体内增殖、凋亡和分化的影响。在体外，TE 增加原代角质形成细胞内钙内流，并上调包括角蛋白 10 在内的各种分化标志物。TE 还特异性增加角质形成细胞中非选择性瞬时受体电位经典（亚型）6（TRPC6）的表达，而敲低 TRPC6 抑制角蛋白 10 的上调。离体，在人皮肤外植体中，TE 在表皮中诱导 TRPC6 的表达，并增加终末分化角质形成细胞的 DNA 片段化。局部用 TE 治疗光化性角化病，代表上皮分化紊乱的原位鳞状细胞癌，导致体内异常 Ki67 表达下调和角蛋白 10 的上调。我们的数据表明，TE 促进角质形成细胞体外和体内的分化。这种作用似乎至少部分通过 TRPC6 介导。
