Abstract 1638: Effect of the phytochemical crinumaquine on prostate mesenchymal type cells

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 1638
• Main Authors: Marvyin, Kristo, Liu, Run-hui, Jin, Huizi, Hua, Yaping, Qu, Yi, Ke, Xisong, Kalland, Karl-Henning, Zhang, Wei-dong, Oyan, Anne Margrete
• Format: Journal Article
• Language: English
• Published: 01-10-2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-1638

In a prostate carcinogenesis cell culture model benign EP156T prostate epithelial cells underwent epithelial to mesenchymal transition (EMT), and a series of progeny EPT mesenchymal type cells accumulated malignant features in a stepwise fashion. Through the screening of phytochemicals using this model, we have found that crinumaquine inhibited proliferation of mesenchymal type EPT1 and EPT2 cells more efficiently than the compound inhibited epithelial type EP156T cells. Genome-wide gene expression analysis revealed a pattern where crinumaquine induced patterns associated with cell cycle arrest at both G1-S and G2-M phase checkpoints and strong up-regulation of genes involved in DNA repair and CDKN1A and CDKN1C and chromatin rearrangement. Differentially expressed genes were uploaded to the Connectivity Map tools (The Broad Institute, MA, USA) and the highest score was associated with histone deacetylase inhibitors. ChemMap analysis based on its chemical structure indicated that crinumaquine targets ER-β and cyclines. Crinumaquine was also found to induce up-regulation of CDH1 and other genes associated with an incomplete mesenchymal to epithelial transition (MET) of EPT1 and EPT2 cells, and this was associated with increased apoptosis markers in gene expression and Western blot analyses. Due to the selective inhibition of mesenchymal type and more malignant cells of the model, crinumaquine will be further explored concerning its anti-cancer leading compound potential.
Citation Format: Kristo Marvyin, Run-hui Liu, Huizi Jin, Yaping Hua, Yi Qu, Xisong Ke, Karl-Henning Kalland, Wei-dong Zhang, Anne Margrete Oyan. Effect of the phytochemical crinumaquine on prostate mesenchymal type cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1638. doi:10.1158/1538-7445.AM2014-1638