Abstract：
As shown by IncuCyte Zoom imaging proliferation assays, invasive triple-negative human breast MDA-MB-231 cancer cells treated with sub-toxic doses (5.0-20 μM, 72 h) of [GaQ3 ] (Q=8-hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical change. This is the first demonstration of potential use of a metal complex in differentiation anti-cancer therapy. Additionally, a trace amount of Cu(II) (0.20 μM) added to the medium dramatically increased [GaQ3 ] cytotoxicity (IC50 ~2 μM, 72 h) due to its partial dissociation and the action of the HQ ligand as a Cu(II) ionophore, as shown with electrospray mass spectrometry and fluorescence spectroscopy assays in the medium. Hence, cytotoxicity of [GaQ3 ] is strongly linked to ligand binding of essential metal ions in the medium, for example, Cu(II). Appropriate delivery mechanisms of such complexes and their ligands could enable a powerful new triple therapeutic approach for cancer chemotherapy, including cytotoxicity against primary tumour, arrest of metastases, and activation of innate and adaptive immune responses.
摘要：
如IncuCyteZoom成像增殖试验所示，亚毒性剂量（5.0-20μM，72h）的[GaQ3]（Q=8-羟基喹啉）引起了深刻的形态变化和细胞迁移的抑制，这可能是由于终末细胞分化或类似的表型变化。这是金属络合物在分化抗癌治疗中的潜在用途的首次证明。此外,向培养基中添加痕量Cu（II）（0.20μM）显着增加[GaQ3]细胞毒性（IC50〜2μM，72h）由于其部分解离和HQ配体作为Cu（II）离子载体的作用，如电喷雾质谱和荧光光谱法在培养基中所示。因此，[GaQ3]的细胞毒性与培养基中必需金属离子的配体结合密切相关，例如，Cu(II)。这种复合物及其配体的适当递送机制可以为癌症化疗提供强大的新的三重治疗方法，包括对原发性肿瘤的细胞毒性，阻止转移，以及先天和适应性免疫反应的激活。
