氧化应激在肿瘤的生存中发挥两重角色，在不同条件下可以促进肿瘤发展或杀死肿瘤细胞。丹卡斯特隆A是从紫菌属真菌Talaromyces purpurogenu中提取的次生代谢物。它在抗前列腺癌化合物筛选中展现了良好的潜力。在本研究中，MTT结果显示丹卡斯特隆A对前列腺癌细胞有细胞毒性作用，对PC-3细胞的IC50为5.098μM，对22Rv1细胞为3.411μM。进一步的研究通过平板成型法和实时细胞分析监测表明丹卡斯特隆A显著抑制了22Rv1和PC-3细胞的克隆结节形成和细胞迁移。此外，流式细胞仪结果显示丹卡斯特隆A诱导前列腺癌细胞凋亡，但对细胞周期分布没有影响。在分子水平上，蛋白质微阵列实验和Western blot分析显示丹卡斯特隆A可特异且显著上调HO-1蛋白表达；细胞荧光染色结果显示丹卡斯特隆A诱导了22Rv1和PC-3细胞反应性氧气体的过度表达。综上所述，丹卡斯特隆A诱导前列腺癌细胞产生强烈的氧化应激反应，导致大量HO-1的产生和大量反应性氧气体的释放，进而导致前列腺癌细胞的凋亡，最终抑制了细胞增殖和迁移。我们还在斑马鱼异种移植瘤模型中验证了丹卡斯特隆A的抗前列腺癌效果。总之，丹卡斯特隆A有潜力作为一种抗前列腺癌药物的开发。版权所有 © 2023. Elsevier B.V. 发布。

Oxidative stress plays a dual role in tumor survival, either promoting tumor development or killing tumor cells under different conditions. Dankasterone A is a secondary metabolite derived from the fungus Talaromyces purpurogenu. It showed good potential in a screen for anti-prostate cancer compounds. In this study, MTT results showed dankasterone A was cytotoxic to prostate cancer cells, with an IC50 of 5.098 μM for PC-3 cells and 3.411 μM for 22Rv1 cells. Further studies, plate cloning assays and real-time cell analysis monitoring showed that dankasterone A significantly inhibited clonal colony formation and cell migration in 22Rv1 and PC-3 cells. In addition, flow cytometry results showed that dankasterone A induced apoptosis in prostate cancer cells while having no impact on cell cycle distribution. At the molecular level, Protein microarray experiments and Western blot assays revealed that dankasterone A specifically and dramatically upregulated HO-1 protein expression; and the results of cell fluorescence staining showed that dankasterone A induced overexpression of reactive oxygen species in 22Rv1 and PC-3 cells. Taken together, dankasterone A induced prostate cancer cells to undergo intense oxidative stress, which resulted in the production of large amounts of HO-1 and the release of large amounts of reactive oxygen species, leading to apoptosis of prostate cancer cells, ultimately resulting in the inhibition of both cell proliferation and migration. We also validated the anti-prostate cancer effects of dankasterone A in vivo in a zebrafish xenograft tumor model. In conclusion, dankasterone A has the potential to be developed as an anti-prostate cancer drug.Copyright © 2023. Published by Elsevier B.V.