Xiangya Hospital of Central South University, Changsha, 410008, P. R. China.
School of Life Sciences, Central South University, Changsha, 410013, P. R. China.
Chem Biodivers. 2023 Jun;20(6):e202201130. doi: 10.1002/cbdv.202201130. Epub 2023 Jun 6.
Currently, prostate cancer is one of the major malignant tumors in males. Recurrence and metastasis are the main obstacles that prevent the effective treatment of prostate cancer. In the present study, we aimed to evaluate emodin (EG) against human prostate cancer PC3 and DU145 cells. Our study showed that EG significantly decreased the cell viability of PC3 and DU145 cells and strikingly induced non-apoptotic cell death via necroptosis that was visualized through colony formation assay, Hoechst 33258 staining, and TEM analysis. Furthermore, RNA-sequencing and KEGG functional enrichment analysis revealed that the necroptosis-related pathway was activated upon EG treatment in PC3 cells. mRNA and protein expression of necroptosis markers were analyzed by qPCR and immunoblotting, which implied that EG-induced cell necroptosis via enhancing the expression of MLKL and HSP90AA1 activating PGAM pathway which is considered as a key mediator of mitochondrial fission and leading to ROS generation in PC3 and DU145 cells. Thus, our findings suggested that EG is a new small molecule agonist that induced necroptosis in prostate cancer cells via the mitochondrial fission HSP90/MLKL/PGAM pathway.
目前，前列腺癌是男性主要的恶性肿瘤之一。复发和转移是阻止前列腺癌有效治疗的主要障碍。在本研究中，我们旨在评估大黄素（EG）对人前列腺癌 PC3 和 DU145 细胞的作用。我们的研究表明，EG 显著降低了 PC3 和 DU145 细胞的细胞活力，并通过坏死性细胞死亡明显诱导非凋亡细胞死亡，这可以通过集落形成试验、Hoechst 33258 染色和 TEM 分析来观察到。此外，RNA 测序和 KEGG 功能富集分析显示，在 PC3 细胞中，EG 处理激活了坏死性细胞死亡相关途径。通过 qPCR 和免疫印迹分析坏死性细胞死亡标志物的 mRNA 和蛋白表达，表明 EG 通过增强 MLKL 和 HSP90AA1 的表达诱导细胞坏死性细胞死亡，从而激活 PGAM 途径，该途径被认为是线粒体分裂的关键介质，导致 PC3 和 DU145 细胞中 ROS 的产生。因此，我们的研究结果表明，EG 是一种新的小分子激动剂，通过线粒体分裂 HSP90/MLKL/PGAM 途径诱导前列腺癌细胞发生坏死性细胞死亡。
