Evaluation of Erastin as a Therapeutic Agent Under Hypoxic Conditions in Pancreatic Cancer Cells
Evaluation of Erastin as a Therapeutic Agent Under Hypoxic Conditions in Pancreatic Cancer Cells
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DOI：
10.21873/anticanres.15424
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发表时间：
2021-11
影响因子：
2
通讯作者：
Satoshi Owada;H. Endo;Yukari Shida;T. Kinoue;Hiroyuki Furuya;M. Tatemichi
中科院分区：
文献类型：
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作者：
Satoshi Owada;H. Endo;Yukari Shida;T. Kinoue;Hiroyuki Furuya;M. Tatemichi
背景/目的：在胰腺癌组织中，由于血流不畅而存在缺氧区域。现有抗癌药物在这些缺氧区域的药理学功效的减弱需要寻找新的抗癌化合物。我们的目的是确定erastin是否在缺氧环境中表现出抗癌作用。材料和方法：胰腺癌细胞系进行氯化钴，缺氧模拟剂。通过细胞活力测定、活性氧测定和蛋白质印迹分析来研究erastin在缺氧环境下的功效。结果：Erastin在缺氧条件下具有明显的细胞毒作用，并能诱导细胞凋亡。此外，erastin触发细胞内积累的活性氧在缺氧环境中。随后的治疗与N-乙酰半胱氨酸，抗氧化剂，显着减弱细胞毒性和细胞凋亡。结论：Erastin通过在缺氧条件下积累细胞内活性氧并诱导细胞凋亡来诱导细胞死亡，证明其作为新型抗癌化合物的进一步开发潜力。
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. Materials and Methods: 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. Results: 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. Conclusion: 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.