Proteomics, Transcriptomics, and Phosphoproteomics Reveal the Mechanism of Talaroconvolutin-A Suppressing Bladder Cancer via Blocking Cell Cycle and Triggering Ferroptosis

作者：Yong Xia, Longquan Xiang, Ming Yao, Zhiying Ai, Wei Yang, Jianhua Guo, Shuhao Fan, Ning Liu, Xiao‐Long Yang · 发表于：Molecular & Cellular Proteomics · 年份：2023 · DOI：10.1016/j.mcpro.2023.100672 · 被引用次数：14 · 研究领域：Bladder and Urothelial Cancer Treatments、Ferroptosis and cancer prognosis、Epigenetics and DNA Methylation

Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng . Whether TalaA exerts anticancer activity in bladder cancer remains unknown. We explored anticancer function and studied the pharmacological mechanism of TalaA from transcriptomic, proteomic, phosphoproteomic, and molecular interaction perspectives. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and western blotting we studied the anticancer activity of TalaA in vitro . For in vivo analysis, we performed xenograft tumor implantation. The anti-tumor effects of TalaA were evaluated through hematoxylin and eosin (H&E) and immunohistochemistry staining and pathological analysis. In high-throughput omics detection, proteomics was conducted to detect changes in the protein profile; transcriptomics was performed used to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. We found TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC 50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 μM respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. In pharmacological mechanism, TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and A...