Characterization of two novel small molecules targeting melanocyte development in zebrafish embryogenesis
Characterization of two novel small molecules targeting melanocyte development in zebrafish embryogenesis
复制标题
斑马鱼胚胎发生过程中两种靶向黑素细胞发育的新型小分子的表征
DOI：
10.1111/j.1755-148x.2012.01007.x
复制
发表时间：
2012-07-01
影响因子：
4.3
通讯作者：
Lin, Shuo
中科院分区：
文献类型：
--
作者：
Chen, Lu;Ren, Xi;Lin, Shuo
黑素细胞是与许多皮肤疾病密切相关的色素细胞，如白癜风、花斑病、Waardenburg综合征和最致命的皮肤癌黑色素瘤。通过对模式生物的研究，已经很好地建立了黑素细胞在胚胎发生过程中发育的遗传调控网络。这个网络似乎也与成人黑素细胞再生和黑色素瘤形成共享。为了鉴定黑素细胞发育和体内平衡的化学调节剂，我们使用斑马鱼胚胎筛选了包含6000种化合物的小分子库，并鉴定了五种抑制色素沉着的新型化合物。在这里，我们报告的两个化合物，12G9和36E9，破坏黑素细胞的发展的特点。TUNEL法检测表明，这两种化合物诱导黑素细胞凋亡。此外，化合物12G9在体外特异性抑制哺乳动物黑素瘤细胞的活力。这两种化合物应可用作研究黑素细胞的化学生物学工具，并可用作对抗黑素细胞相关疾病的候选药物。
Melanocytes are pigment cells that are closely associated with many skin disorders, such as vitiligo, piebaldism, Waardenburg syndrome, and the deadliest skin cancer, melanoma. Through studies of model organisms, the genetic regulatory network of melanocyte development during embryogenesis has been well established. This network also seems to be shared with adult melanocyte regeneration and melanoma formation. To identify chemical regulators of melanocyte development and homeostasis, we screened a small‐molecule library of 6000 compounds using zebrafish embryos and identified five novel compounds that inhibited pigmentation. Here we report characterization of two compounds, 12G9 and 36E9, which disrupted melanocyte development. TUNEL assay indicated that these two compounds induced apoptosis of melanocytes. Furthermore, compound 12G9 specifically inhibited the viability of mammalian melanoma cells in vitro. These two compounds should be useful as chemical biology tools to study melanocytes and could serve as drug candidates against melanocyte‐related diseases.