Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Anticancer Agents Med Chem. 2020;20(16):1956-1965. doi: 10.2174/1871520620666200508085439.
Highly aggressive and resistant to chemotherapy, pancreatic cancers are the fourth leading cause of cancer-related deaths in the western world. The absence of effective chemotherapeutics is leading researchers to develop novel drugs or repurpose existing chemicals. Alexidine Dihydrochloride (AD), an orally bioavailable bis-biguanide compound, is an apoptosis stimulating reagent. It induces mitochondrial damage by inhibiting a mitochondrial-specific protein tyrosine phosphatase, PTPMT1. The aim of this study was to test AD as a novel compound to induce apoptosis in a human pancreatic adenocarcinoma cell lines, Panc-1, MIA PaCa-2, AsPC-1, and Psn-1.
After the IC50 value of the AD was determined by cytotoxicity assay, apoptosis was observed by a variety of methods, including the detection of early apoptosis marker Annexin V and the proteomic profile screening by apoptosis array. Multicaspase and mitochondrial depolarization were measured, and changes in the cell cycle were analyzed.
AD is found to initiate apoptosis by activating the intrinsic pathway and inhibit the cell cycle in pancreatic cancer cell lines.
In conclusion, considering its anti-cancer properties and bioavailability, Alexidine dihydrochloride can be considered as a potential candidate against pancreatic adenocarcinomas.
胰腺癌侵袭性强，对化疗耐药，是西方世界癌症相关死亡的第四大主要原因。由于缺乏有效的化疗药物，研究人员正在开发新的药物或重新利用现有化学品。盐酸阿地西林（AD）是一种口服生物利用度的双胍化合物，是一种凋亡刺激试剂。它通过抑制一种线粒体特异性的蛋白酪氨酸磷酸酶 PTPMT1 来诱导线粒体损伤。本研究旨在测试 AD 作为一种诱导人胰腺腺癌细胞系（Panc-1、MIA PaCa-2、AsPC-1 和 Psn-1）凋亡的新型化合物。
通过细胞毒性测定确定 AD 的 IC50 值后，通过多种方法观察细胞凋亡，包括检测早期凋亡标志物 Annexin V 和通过凋亡阵列筛选蛋白质组特征谱。测量多半胱氨酸酶和线粒体去极化，并分析细胞周期的变化。
AD 通过激活内在途径启动细胞凋亡，并抑制胰腺癌细胞系的细胞周期。
综上所述，考虑到其抗癌特性和生物利用度，盐酸阿地西林可被视为一种针对胰腺腺癌的潜在候选药物。
