鲁索利替尼
托法替尼
贾纳斯激酶
化学
骨髓纤维化
Janus激酶抑制剂
磷酸二酯键
核酸
癌症研究
生物化学
信号转导
生物
核糖核酸
免疫学
骨髓
类风湿性关节炎
基因
作者
Jeeraprapa Siriwaseree,Kamonpan Sanachai,Thitinan Aiebchun,Lueacha Tabtimmai,Buabarn Kuaprasert,Kiattawee Choowongkomon
出处
期刊:ACS omega
[American Chemical Society]
日期:2022-06-23
卷期号:7 (26): 22797-22803
被引量:1
标识
DOI:10.1021/acsomega.2c02404
摘要
Janus kinase (JAK) deregulation of the JAK/signal transducers and activators of transcription pathway leads to myelofibrosis that can be treated by JAK inhibitors including Ruxolitinib and Tofacitinib. Even though both inhibitors are effective against myelofibrosis, each of them has a different mode of action in the cells. Ruxolitinib is an inhibitor for selective JAK1/2, and Tofacitinib is an inhibitor for JAK3. This study evaluated the chemical fingerprints of TF-1 cells after JAK inhibitor treatments by the synchrotron Fourier transform infrared microspectroscopy (S-FTIR) spectrum. Tofacitinib and Ruxolitinib treatments in TF-1 cells were applied with a chemical fingerprint approach in S-FTIR spectroscopy and in vitro cytotoxicity in a cell-based assay. Principal component analysis or PCA was utilized to classify three cell treatments with three biochemical alteration absorbances of lipid vibration by the C–H stretching, protein amide I that appeared from the C═O stretching, and a P═O phosphodiester bond from nucleic acids. The results showed that the inhibition effect of Ruxolitinib on the TF-1 cell lines was two-fold higher than Tofacitinib. PCA distinguishes untreated and drug-treated cells by detecting cellular biochemical alteration. The loading plots identify that proteins and nucleic acids were the different main components in disparate cell treatments. Tofacitinib was distinct from the others in lipid and nucleic acid. The second derivative spectra of the three molecular components had decreased lipid production and accumulation, changes in secondary structures in proteins, and a high level of RNA overexpression in cell treatment. The JAK inhibitors caused different spectroscopic biomarkers of the modifications of secondary protein conformation, stimulated cell lipid accumulation, and phosphorylation from untreated cells. The alteration of cellular biochemical components suggests that FTIR is a potential tool to analyze specific patterns of drug cellular responses at the molecular level.
科研通智能强力驱动
Strongly Powered by AbleSci AI