青萼藻素A直接靶向抗氧化酶PRDX1和PRDX2,通过ros介导的自噬诱导肾癌细胞毒性

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Yaping Niu, Jinhuan Ou, Xiaoru Zhong, Piao Luo, Junhui Chen, Ashok Iyaswamy, Haibo Tong, Zhou Zhu, Peng Chen, Xu Wei, Wei Zhang, Hualin Ma, Yulin Feng, Chuanbin Yang, Jigang Wang
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引用次数: 0

摘要

青萼花素A (Glaucocalyxin A, GLA)是一种从药用植物鸢尾草(Rabdosia japonica)中提取的生物活性二萜类化合物,具有较强的抗肿瘤活性,但其在肾细胞癌(RCC)中的分子机制尚不清楚。在这里,据报道GLA通过活性氧(ROS)过度积累触发RCC细胞毒性。从机制上讲,ROS激增激活了自噬,而药物或基因自噬抑制显著地挽救了gla诱导的细胞死亡,表明自噬在这种情况下起着促死亡的作用。利用基于活性的蛋白谱分析(ABPP)和蛋白质组学分析,我们确定过氧化物还毒素PRDX1/2是GLA的直接共价靶点。功能验证表明,PRDX1/2过表达可减轻gla介导的细胞凋亡,确立其作为控制细胞命运的关键氧化还原传感器的作用。研究结果描绘了PRDX1/2靶向驱动的ros -自噬-凋亡轴,将GLA定位为RCC治疗的新型治疗支架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Glaucocalyxin A Induces Cytotoxicity in Renal Cancer Cells via ROS-Mediated Autophagy by Direct Targeting of Antioxidant Enzymes PRDX1 and PRDX2.

Glaucocalyxin A (GLA), a bioactive diterpenoid from the medicinal plant Rabdosia japonica, demonstrates potent antitumor activity, yet its molecular mechanisms in renal cell carcinoma (RCC) remain elusive. Here, GLA is reported to trigger cytotoxicity in RCC cells through reactive oxygen species (ROS) overaccumulation. Mechanistically, ROS surge activates autophagy, and pharmacological or genetic autophagy inhibition significantly rescues GLA-induced cell death, indicating autophagy acts as a pro-death effector in this context. Employing activity-based protein profiling (ABPP) coupled with proteomic analysis, peroxiredoxins PRDX1/2 are identified as direct covalent targets of GLA. Functional validation reveals that PRDX1/2 overexpression mitigates GLA-mediated apoptosis, establishing their role as critical redox sensors governing cell fate. The findings delineate a ROS-autophagy-apoptosis axis driven by PRDX1/2 targeting, positioning GLA as a novel therapeutic scaffold for RCC treatment.

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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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