Gene profiling of HepG2 cells following nitidine chloride treatment: An investigation with microarray and Connectivity Mapping.

ABSTRACT: Nitidine chloride (NC), an inartificial bioactive alkaloid present in the root of Zanthoxylum nitidum (Roxb.) DC, is known for its versatile anti?inflammation and anticancer capabilities. The molecular mechanisms underlying its anticancer properties, however, remain obscure. The authors of the present study demonstrated the tumor suppressive effects of NC in a human liver cancer cell line using an MTT assay. The tumor suppressive capacity of NC was also analysed in a tumor xenograft nude mouse model. Changes in tumor cell gene expression profiles following NC treatment were detected by microarray; bioinformatics analysis demonstrated that differentially expressed genes were enriched in several cancer?associated pathways, including those initiated by transforming growth factor?? and phosphatidylinositol 4,5?bisphosphate 3?kinase/RAC?? serine/threonine?protein kinase signaling. A Connectivity Map revealed that parthenolide, which has been identified previously as possessing anti?inflammatory and anticancer functions, was potentially extremely similar in molecular function to NC. By screening the data from The Cancer Genome Atlas project, eight genes that were upregulated in liver cancer and significantly suppressed by NC treatment were identified. Overexpression of these genes was closely associated with advanced tumor stage and poor differentiation status. This combination of upregulated genes enabled successful identification and prediction of prognosis for liver cancer. The findings of the present study suggest that NC could inhibit the growth of liver cancer cells through several potential molecular targets and signaling pathways.

SUBMITTER: Liu LM 

PROVIDER: S-EPMC6489000 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature