Albrecht-Kossel-Institute for Neuroregeneration, Center for Mental Health, University of Rostock, Germany.
Biochem Pharmacol. 2013 Mar 15;85(6):763-71. doi: 10.1016/j.bcp.2012.12.013. Epub 2012 Dec 26.
Indolylmaleimides display a broad spectrum of biological activity and offer great opportunity to influence several aspects of cell fate, as proliferation and differentiation. In this study we describe the effect of PDA-66, a newly synthesised indolylmaleimide, showing a strong dose dependent anti-proliferative effect on immortalised human progenitor and cancer cells. We demonstrated a highly depolymerizing effect on in vitro tubulin assembly and conclude that PDA-66 acts as microtubule destabilising agent. In addition we found that PDA-66 induces mitotic arrest of cells in the G₂/M phase of the cell cycle. Subsequently cells undergo apoptosis, indicating the major mechanism of the anti-proliferative effect. To prove a potential anti-cancer activity of PDA-66 we examined the effect of PDA-66 on human SH-SY5Y neuroblastoma and A-459 lung cancer cells, showing a significant reduction in cancer cell proliferation in a dose dependent manner. Thus PDA-66 is a new anti-mitotic compound with an indole-core with the potential to be used for cancer therapy.
吲哚马来酰亚胺具有广泛的生物活性，为影响细胞命运的多个方面，如增殖和分化，提供了巨大的机会。在这项研究中，我们描述了 PDA-66 的作用，PDA-66 是一种新合成的吲哚马来酰亚胺，对永生化的人祖细胞和癌细胞表现出强烈的剂量依赖性抗增殖作用。我们证明了它对体外微管组装有很强的解聚作用，并得出结论，PDA-66 作为微管去稳定化剂发挥作用。此外，我们发现 PDA-66 诱导细胞在细胞周期的 G₂/M 期有丝分裂停滞。随后细胞发生凋亡，表明其具有显著的抗增殖作用。为了证明 PDA-66 的潜在抗癌活性，我们研究了 PDA-66 对人 SH-SY5Y 神经母细胞瘤和 A-459 肺癌细胞的影响，结果表明 PDA-66 以剂量依赖的方式显著抑制癌细胞增殖。因此，PDA-66 是一种具有吲哚核心的新型抗有丝分裂化合物，具有用于癌症治疗的潜力。
