Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan
Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
Anticancer Res. 2021 Dec;41(12):6051-6059. doi: 10.21873/anticanres.15424.
BACKGROUND/AIM: In pancreatic cancer tissues, hypoxic areas exist due to poor blood flow. Attenuation of the pharmacological efficacy of existing anticancer drugs in these hypoxic areas necessitates the search for novel anticancer compounds. We aimed to determine whether erastin exhibits anticancer effects in a hypoxic environment.
Pancreatic cancer cell lines were subjected to cobalt chloride, a hypoxia-mimicking agent. Cell viability assay, measurement of reactive oxygen species, and western blotting analysis were conducted to investigate the efficacy of erastin under hypoxic environments.
Erastin exhibited remarkable cytotoxicity and induced apoptosis under hypoxic conditions. Furthermore, erastin triggered the intracellular accumulation of reactive oxygen species in a hypoxic environment. Subsequent treatment with N-acetylcysteine, an antioxidant, markedly attenuated cytotoxicity, and apoptosis.
Erastin induces cell death by accumulation of intracellular reactive oxygen species and inducing apoptosis under hypoxic conditions, proving its potential for further development as a novel anticancer compound.
背景/目的:由于血流不畅,胰腺癌组织中存在缺氧区域。这些缺氧区域会降低现有抗癌药物的药理功效,因此需要寻找新的抗癌化合物。本研究旨在确定依瑞替康在缺氧环境中是否具有抗癌作用。
采用钴氯化物模拟缺氧环境处理胰腺癌细胞系。通过细胞活力测定、活性氧检测和 Western blot 分析来研究依瑞替康在缺氧环境中的疗效。
依瑞替康在缺氧条件下表现出显著的细胞毒性和诱导凋亡作用。此外,依瑞替康在缺氧环境下会引发细胞内活性氧的积累。随后用抗氧化剂 N-乙酰半胱氨酸处理,可显著减轻细胞毒性和凋亡。
依瑞替康通过在缺氧条件下积累细胞内活性氧并诱导细胞凋亡导致细胞死亡,证明其具有进一步开发为新型抗癌化合物的潜力。