Kemény-Beke Adám, Aradi János, Damjanovich Judit, Beck Zoltán, Facskó Andrea, Berta András, Bodnár Andrea
Department of Ophthalmology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
Cancer Lett. 2006 Jun 8;237(1):67-75. doi: 10.1016/j.canlet.2005.05.037. Epub 2005 Jul 12.
The benzophenanthridine alkaloids sanguinarine, chelerythrine and chelidonine were reported previously to provoke cell death in a variety of tumor cells suggesting their potential application as anticancer agents. Here we tested their effects on a primary human uveal melanoma cell line, OCM-1. Flow cytometric analysis of annexin V binding/PI exclusion and DNA fragmentation disclosed that all these alkaloids could induce apoptosis in OCM-1 cells. Moreover, necrotic cell death was also observed upon alkaloid treatment. As it was also evidenced by light microscopic inspection of cellular morphology, chelidonine primarily caused apoptosis, while sanguinarine and chelerythrine were effective via a so-termed bimodal cell death (apoptosis and primary necrosis). The relative efficiencies of the two modes depended on the applied dose. This study is the first implication for the possible use of these alkaloids in the therapy of uveal melanomas, for which no really efficient therapeutic regimen is available so far.
据此前报道,苯并菲啶生物碱血根碱、白屈菜红碱和白屈菜碱可在多种肿瘤细胞中引发细胞死亡,这表明它们作为抗癌剂具有潜在应用价值。在此,我们测试了它们对原发性人葡萄膜黑色素瘤细胞系OCM-1的影响。通过膜联蛋白V结合/碘化丙啶排除法和DNA片段化的流式细胞术分析表明,所有这些生物碱均可诱导OCM-1细胞凋亡。此外,在用生物碱处理后也观察到了坏死性细胞死亡。细胞形态的光学显微镜检查也证实,白屈菜碱主要引起凋亡,而血根碱和白屈菜红碱则通过所谓的双峰细胞死亡(凋亡和原发性坏死)发挥作用。两种模式的相对效率取决于所施用的剂量。本研究首次表明这些生物碱可能用于葡萄膜黑色素瘤的治疗,目前尚无真正有效的治疗方案。