Quantitative analysis of differential protein expression in cervical carcinoma cells after zeylenone treatment by stable isotope labeling with amino acids in cell culture

• The first study of anti-tumor effect on human cervical cancer cells by zeylenone
• The first application of proteomics to analyze the differences of protein expression of cervical cancer cell
• 14-3-3 protein family were first discovered the differences in human cervical cancer cells.
• 17 differentially expressed proteins were identified by HPLC–MS/MS.

Cervical carcinoma is a malignant tumor that poses a serious threat to women's health and survival. Approximately 10–25% of cervical cancers are adenocarcinomas (ACs). AC has high rates of recurrence and mortality, while there is no effective treatment for now. Zeylenone (Zey), which is isolated from an ethanol extract of the leaves of Uvaria grandiflora Roxb. of the family Annonaceae, has shown potent inhibitory activity against various tumor cells, including cervical carcinoma cells. To gain insight into the molecular mechanism underlying the effect of Zey on AC, we quantified protein expression changes in AC cells treated with Zey. We used stable isotope labeling with amino acids in cell culture (SILAC) in combination with high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC–ESI–MS/MS) and bioinformatics analysis to compare protein expression profiles in HeLa cells before and after Zey treatment. Of 1805 differentially expressed proteins identified, 229 were screened as key protein molecules and classified into nine categories. Profiling of differentially-expressed proteins contributed to our understanding of the molecular mechanism by which Zey induces HeLa cell apoptosis. Using this method, candidate targets can be identified for developing new drugs against cervical carcinoma.

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