PDF(Pubmed)
Abstract：
Due to its emerging resistance to current therapies, colon cancer remains one of the most difficult types of cancer to treat. Silver, a non-invasive metal, is well-known for its antimicrobial and anti-cancer properties. Two novel silver(I) phosphine complexes, [silver(I) diphenyl-2-pyridylphosphine]Br (1) and [silver(I) is 4-(dimethylamino)phenyldiphenylphosphine]Br (2), were synthesized and characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance (1H, 13C, 31P). To assess the complexes\' potentials as antiproliferative agents, experiments were conducted on human colorectal cancer cells (HT-29) in vitro. The evaluation involved the analysis of morphological changes, the performance of an alamarBlue® proliferation assay, and the undertaking of flow cytometric analyses to detect mitochondrial alterations. Complex 1 displayed superior selectivity and significant inhibitory effects on malignant HT-29 cells while exhibiting minimal toxicity towards two non-malignant HEK-293 and MRHF cells. Moreover, after 24 h of treatment, complex 1 (IC50, 7.49 µM) demonstrated higher efficacy in inhibiting cell proliferation compared with complex 2 (IC50, 21.75 µM) and CDDP (IC50, 200.96 µM). Flow cytometric studies indicated that complex 1 induced regulated cell death, likely through mitochondrial-mediated apoptosis. Treatment with complex 1 induced morphological changes indicative of apoptosis, which includes membrane blebbing, PS externalization, increased levels of reactive oxygen species (ROS) and mitochondrial membrane depolarization (ΔΨm). These observations suggest that complex 1 targets the mitochondria and holds promise as a novel metal-based anti-cancer therapeutic for the selective treatment of colorectal cancer.
摘要：
由于其对当前疗法的新兴抵抗，结肠癌仍然是最难治疗的癌症之一。银色,一种非侵入性金属，以其抗菌和抗癌特性而闻名。两种新颖的银（I）膦配合物，[二苯基-2-吡啶基膦银(I)]Br(1)和[银(I)是4-(二甲基氨基)苯基二苯基膦]Br(2)，合成并通过元素分析表征，红外光谱,和核磁共振(1H，13C,31P）。为了评估复合物作为抗增殖剂的潜力，实验是在体外对人大肠癌细胞（HT-29）进行的。评估涉及形态变化的分析，alamarBlue®增殖试验的性能，以及进行流式细胞术分析以检测线粒体改变。复合物1对恶性HT-29细胞表现出优异的选择性和显着的抑制作用，同时对两种非恶性HEK-293和MRHF细胞表现出最小的毒性。此外，治疗24小时后，与复合物2（IC50，21.75µM）和CDDP（IC50，200.96µM）相比，复合物1（IC50，7.49µM）在抑制细胞增殖方面表现出更高的功效。流式细胞术研究表明，复合物1诱导调节细胞死亡，可能通过线粒体介导的细胞凋亡。用复合物1处理诱导的指示细胞凋亡的形态学变化，其中包括膜起泡，PS外部化，活性氧（ROS）和线粒体膜去极化（ΔkWm）水平升高。这些观察结果表明，复合物1靶向线粒体，有望作为一种新型的基于金属的抗癌治疗剂，用于选择性治疗结直肠癌。
