Betulinic acid induces apoptosis in skin cancer cells and differentiation in normal human keratinocytes
Betulinic acid induces apoptosis in skin cancer cells and differentiation in normal human keratinocytes
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DOI：
10.1111/j.1600-0625.2005.00352.x
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发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Dräger, B
中科院分区：
文献类型：
--
作者：
Galgon, T;Wohlrab, W;Dräger, B
桦木酸 (BA) 是一种植物来源的五环三萜，可诱导黑色素瘤细胞和其他神经外胚层来源的恶性细胞死亡。对于正常靶细胞中的其他生物学效应知之甚少。我们在这项研究中表明，BA 会诱导正常人角质形成细胞 (NHK) 的分化和细胞死亡。在正常人角质形成细胞、HaCaT 细胞、IGR1 黑色素瘤细胞和正常黑色素细胞中比较了 BA 的细胞毒性特征。正如预期的那样，BA 对所有细胞类型（正常细胞和恶性细胞）都具有毒性，但其细胞毒性效力以及在四种不同皮肤细胞类型中诱导细胞凋亡与坏死细胞死亡的程度各不相同。细胞凋亡通过膜联蛋白 V 和 Apo2.7 结合以及 DNA 片段化来证明。证明了角质形成细胞中分化相关抗原（丝聚蛋白和外皮蛋白）的诱导，以及处理的细胞培养物中的特定形态变化。 BA 除了在细胞系统中具有细胞毒活性外，还能够诱导 NHK 分化为角质细胞，而不会立即引起细胞凋亡。
Betulinic acid (BA), a pentacyclic triterpene of plant origin, induces cell death in melanoma cells and other malignant cells of neuroectodermal origin. Little is known about additional biological effects in normal target cells. We show, in this study, that BA induces differentiation as well as cell death in normal human keratinocytes (NHK). Cytotoxicity profiles of BA are compared among normal human keratinocytes, HaCaT cells, IGR1 melanoma cells and normal melanocytes. As expected, BA is toxic to all cell types, normal and malignant, but varies in its cytotoxic potency and in the extent of induction of apoptotic vs. necrotic cell death in the four different skin cell types. Apoptosis is proved by annexin V and Apo2.7 binding and by DNA fragmentation. Induction of differentiation-associated antigens in keratinocytes - filaggrin and involucrin - is demonstrated, together with specific morphological changes in treated cell cultures. BA, apart from its cytotoxic activities in cellular systems, is capable of inducing differentiation of NHK into corneocytes without immediately provoking apoptotic cell death.