PDF(Pubmed)
Abstract：
This study demonstrated the anticancer efficacy of chalcones with indole moiety (MIPP, MOMIPP) in fibrosarcoma cells for the first time. The results showed that MIPP and MOMIPP reduced the viability of HT-1080 cells in a concentration-dependent manner. MOMIPP was more active than MIPP in HT-1080 cells, showing lower IC50 values (3.67 vs. 29.90 μM). Both compounds at a concentration of 1 μM induced apoptosis in HT-1080 cells, causing death strictly related to caspase activation, as cell viability was restored when the caspase inhibitor Z-VAD was added. Reactive oxygen species production was approximately 3-fold higher than in control cells, and cotreatment with the inhibitor of mitochondrial ATPase oligomycin diminished this effect. Such effects were also reflected in mitochondrial dysfunction, including decreased membrane potential. Interestingly, the compounds that were studied caused massive vacuolization in HT-1080 cells. Immunocytochemical staining and TEM analysis showed that HT-1080 cells exhibited increased expression of the LC3-II protein and the presence of autophagosomes with a double membrane, respectively. Both compounds induced apoptosis, highlighting a promising link between autophagy and apoptosis. This connection could be a new target for therapeutic strategies to overcome chemoresistance, which is a significant cause of treatment failure and tumour recurrence in fibrosarcoma following traditional chemotherapy.
摘要：
这项研究证明了具有吲哚部分的查耳酮的抗癌功效（MIPP，MOMIPP）首次在纤维肉瘤细胞中。结果表明，MIPP和MOMIPP以浓度依赖的方式降低HT-1080细胞的活力。在HT-1080细胞中，MOMIPP比MIPP更活跃，显示较低的IC50值(3.67vs.29.90μM)。浓度为1μM的两种化合物均可诱导HT-1080细胞凋亡，导致与胱天蛋白酶激活密切相关的死亡，当加入胱天蛋白酶抑制剂Z-VAD时,细胞活力恢复。活性氧的产量比对照细胞高约3倍，与线粒体ATP酶寡霉素抑制剂的共同治疗减弱了这种作用。这种影响也反映在线粒体功能障碍中，包括降低的膜电位。有趣的是,研究的化合物在HT-1080细胞中引起大量空泡化。免疫细胞化学染色和TEM分析表明，HT-1080细胞表现出LC3-II蛋白的表达增加和具有双膜的自噬体的存在，分别。两种化合物均可诱导细胞凋亡，强调自噬和细胞凋亡之间有希望的联系。这种联系可能是克服化学抗性的治疗策略的新目标，这是传统化疗后纤维肉瘤治疗失败和肿瘤复发的重要原因。
