研究动态
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一种新型的染料苷衍生物通过促进人胰腺癌细胞的凋亡性细胞死亡来发挥抗癌作用。

A novel chalcone derivative exerts anticancer effects by promoting apoptotic cell death of human pancreatic cancer cells.

发表日期:2023 Aug 23
作者: Suji Baek, Sanghee Nah, Joo Yeon Park, Sang Ju Lee, Yong Gil Kang, Seung Hae Kwon, Seung Jun Oh, Kang Pa Lee, Byung Seok Moon
来源: Cell Death & Disease

摘要:

侵袭性胰腺癌通常采用化疗药物来在手术前减小肿瘤并在手术后防止转移,同时结合外科手段进行治疗。本研究中,我们合成了一种含有羟基的香豆素衍生物(1,IC50 = 32.1 μM),并通过评估其对BXPC-3癌细胞的诱导凋亡作用来研究其作为抗癌药物候选药物的潜力。使用可溶于水的四唑化合物1试剂测量了1处理的BXPC-3细胞的存活率。经过1诱导的BXPC-3细胞使用不同探针或抗体进行了染色,如乙烯基高丝染料-1,Hoechst,抗-Ki67和MitoTracker。蛋白质表达通过免疫印迹法进行测量,mRNA表达通过实时聚合酶链反应进行确定。使用刺激拉曼散射显微分析直接监测到凋亡分子特征,如脂质积累和蛋白质降解。通过对1的孵育时间和浓度依赖性研究,我们发现它显著减少了BXPC-3细胞的增殖,并增加了凋亡细胞的数量。化合物1诱导了线粒体功能障碍,p38的磷酸化以及caspase 3的剪切。这些结果表明1是胰腺癌的潜在治疗药物,为新型抗癌药物候选药物的开发提供了有价值的见解。版权所有 © 2023 Elsevier Ltd。保留所有权利。
Aggressive pancreatic cancer is typically treated using chemotherapeutics to reduce the tumor pre-operatively and prevent metastasis post-operatively, as well as surgical approaches. In the present study, we synthesized a hydroxyl group-introduced chalcone derivative (1, IC50 = 32.1 μM) and investigated its potential as an anticancer drug candidate by evaluating its apoptosis-promoting effects on BXPC-3 cancer cells. The viability of BXPC-3 cells treated with 1 was measured using the water-soluble tetrazolium 1 reagent. BXPC-3 cells induced by 1 were stained with diverse probes or antibodies, such as ethidium homodimer-1, Hoechst, anti-Ki67, and MitoTracker. Protein expression was measured using an immunoblotting assay, and mRNA expression was determined using real-time polymerase chain reaction. Apoptotic molecular features, such as lipid accumulation and protein degradation, were monitored directly using stimulated Raman scattering microspectroscopy. Through incubation time- and concentration-dependent studies of 1, we found that it significantly reduced the proliferation and increased the number of apoptotic BXPC-3 cells. Compound 1 induced mitochondrial dysfunction, phosphorylation of p38, and caspase 3 cleavage. These results indicate that 1 is a potential therapeutic agent for pancreatic cancer, providing valuable insights into the development of new anticancer drug candidates.Copyright © 2023 Elsevier Ltd. All rights reserved.