Galgon Tino, Wohlrab Wolfgang, Dräger Birgit
Faculty of Pharmacy, Institute of Pharmaceutical Biology and Pharmacology, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
Exp Dermatol. 2005 Oct;14(10):736-43. doi: 10.1111/j.1600-0625.2005.00352.x.
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.
桦木酸（BA）是一种植物源五环三萜，可诱导黑色素瘤细胞及其他神经外胚层来源的恶性细胞发生细胞死亡。关于其在正常靶细胞中的其他生物学效应，人们了解甚少。在本研究中，我们发现BA可诱导正常人角质形成细胞（NHK）分化以及细胞死亡。比较了BA在正常人角质形成细胞、HaCaT细胞、IGR1黑色素瘤细胞和正常黑素细胞中的细胞毒性特征。正如预期的那样，BA对所有细胞类型（正常和恶性）均有毒性，但在四种不同皮肤细胞类型中，其细胞毒性效力以及诱导凋亡与坏死性细胞死亡的程度有所不同。通过膜联蛋白V和Apo2.7结合以及DNA片段化证明了细胞凋亡。证明了角质形成细胞中与分化相关的抗原——丝聚蛋白和兜甲蛋白的诱导，以及处理后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性活性外，还能够诱导NHK分化为角质形成细胞，而不会立即引发凋亡性细胞死亡。
