Integrative bioinformatics analysis reveals possible targets and mechanism of ellipticine in inhibiting breast cancer stem cells

Abstract

Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an alkaloid from Ochrosia elliptica, can reduce the growth and inhibit the self-renewal of ALDH1A1-positive breast cancer stem cells (BCSCs); however, the molecular mechanisms of this compound remain unclear. In this study, we use bioinformatics to explore the potential targets and molecular mechanisms of ellipticine in BCSCs. The expression of genes related to the sensitivity of cancer cells toward ellipticine was obtained from COMPARE. A list of genes related to BCSCs was retrieved from Pubmed by using the keywords “Homo sapiens, breast cancer stem cells.” Protein-protein interaction (PPI) network, Gene Ontology (GO), and KEGG pathway enrichment analyses were performed using STRING-DB. Gene alterations were analyzed using cBioPortal. The prognostic value of the selected genes was evaluated by Kaplan–Meier survival curves. Two genes that are affected by ellipticine and related to BCSCs, namely, XRCC5 and CD59, were selected using a Venn diagram of the COMPARE and PubMed data. Ellipticine may target the complement cascade and DNA repair mechanism in BCSCs. More importantly, XRCC5 and CD59 appear to be potential targets and biomarkers for evaluating the bioactivity of ellipticine in BCSCs. The results of this study are useful for elucidating the molecular mechanism and role of ellipticine in BCSCs.