Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning 530200, China; Guangxi Key Laboratory of Marine Drugs, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning 530200, China.
Eur J Pharmacol. 2023 Oct 15;957:175988. doi: 10.1016/j.ejphar.2023.175988. Epub 2023 Aug 18.
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 IC of 5.10 μM for PC-3 cells and 3.41 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.
氧化应激在肿瘤存活中具有双重作用，即在不同条件下促进肿瘤发展或杀死肿瘤细胞。Dankasterone A 是一种从真菌 Talaromyces purpurogenu 衍生的次级代谢产物。它在抗前列腺癌化合物的筛选中表现出良好的潜力。在这项研究中，MTT 结果表明 dankasterone A 对前列腺癌细胞具有细胞毒性，对 PC-3 细胞的 IC 为 5.10 μM，对 22Rv1 细胞的 IC 为 3.41 μM。进一步的研究，平板克隆实验和实时细胞分析监测表明，dankasterone A 显著抑制 22Rv1 和 PC-3 细胞的克隆集落形成和细胞迁移。此外，流式细胞术结果表明 dankasterone A 诱导前列腺癌细胞凋亡，而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 分析表明，dankasterone A 特异性且显著地上调 HO-1 蛋白表达；细胞荧光染色的结果表明 dankasterone A 诱导 22Rv1 和 PC-3 细胞中活性氧的过表达。综上所述，dankasterone A 诱导前列腺癌细胞经历强烈的氧化应激，导致大量 HO-1 的产生和大量活性氧的释放，导致前列腺癌细胞凋亡，最终抑制细胞增殖和迁移。我们还在斑马鱼异种移植肿瘤模型中验证了 dankasterone A 的抗前列腺癌作用。总之，dankasterone A 具有开发为抗前列腺癌药物的潜力。
