Department of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
Affiliated Hospital of Binzhou Medical University, Yantai, China.
Anticancer Agents Med Chem. 2019;19(4):515-527. doi: 10.2174/1871520619666190212124339.
Peniciketal A (Pe-A), a spiroketal compound, shows potent anticancer activities in human acute monocytic leukemia. However, the detailed mechanisms and potent targets of Pe-A remain largely unexplored. Here, we investigated the differentially expressed proteins between the Pe-A-treated group and the control group on human acute monocytic leukemia cell line THP-1.
The DEPs were analyzed by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label. The function and feature of the identified proteins were analyzed by the bioinformatic analysis. Western blotting was used to evaluate protein expression.
The DEPs were primarily sub located in the cytoplasm and the nucleus by regulating 21 pathways enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, we preliminarily demonstrated that glucose-6-phosphate 1-dehydrogenase (G6PD), prolow-density lipoprotein receptor-related protein 1 (LRP1) and Calreticulin (CALR) might be the potent targets of Pe-A on death induction of THP-1 cells.
Collectively, this study not only provides a global proteomic profile as the supplementary data of our previous studies but also provides interesting information that Pe-A may exert more bio-activities.
Peniciketal A（Pe-A）是一种螺缩酮化合物，在人类急性单核细胞白血病中显示出很强的抗癌活性。然而，Pe-A 的详细机制和有效靶点在很大程度上仍未得到探索。在这里，我们研究了 Pe-A 处理组和对照组之间人急性单核细胞白血病细胞系 THP-1 的差异表达蛋白。
采用 TMT 标记的液相色谱-串联质谱（LC-MS/MS）分析 DEPs。通过生物信息学分析对鉴定出的蛋白质的功能和特征进行分析。Western blotting 用于评估蛋白质表达。
通过京都基因与基因组百科全书（KEGG）富集的 21 条途径，差异表达蛋白主要位于细胞质和细胞核中。此外，我们初步表明，葡萄糖-6-磷酸 1-脱氢酶（G6PD）、前低密度脂蛋白受体相关蛋白 1（LRP1）和钙网蛋白（CALR）可能是 Pe-A 诱导 THP-1 细胞死亡的有效靶点。
综上所述，本研究不仅提供了我们之前研究的补充性全蛋白质组图谱，还提供了有趣的信息，表明 Pe-A 可能具有更多的生物活性。
