Antitumor lectin from Sclerotium rolfsii (SRL) induces apoptosis in human colon cancer HT29 cells by activation of multiple signaling pathways; A microarray analysis

ABSTRACT: TF antigen specific Sclerotium rolfsii lectin (SRL) induces apoptosis in human colon cancer HT29 cells and has tumour suppressing effect in vivo as reported earlier. In this study, we investigated the signaling pathways to identify the signature genes that lead to apoptosis of HT29 cells by mRNA and miRNA microarray analysis. HT29 cells were treated with SRL (20 ug/ml) for 2, 4, 8 12, 24 and 48h and gene expression microarray analysis was performed using SurePrint G3 Human Gene Expression Microarray kit. Several hundred entities were differentially regulated with a fold change value of greater than or equal to 2 and p value less than or equal to 0.05 following interaction of SRL at all-time points. Pathway analysis using GeneSpring 12.6.1 revealed that the MAPK signaling pathway is affected as early as 2h while cell cycle, DNA replication and apoptosis pathways are most significantly affected at 24 and 48h. SRL induced immediate over-expression of the transcription factor c-Jun as early as 2h. Very few miRNAs were found to be differentially regulated at 2 and 4h, however, a significant change in differentially expressed miRNAs were noticed at 12h with the miRNA gene target list significantly overlapping with the differential gene expression. The study suggests that the interaction of SRL with HT29 cells triggers apoptosis by affecting cell cycle, DNA replication and apoptosis signaling pathways. The observed effects may be initiated by affecting MAP kinase pathway and mediated by c-JUN. These findings were further validated by qRT-PCR and western blotting. The findings will enable to exploit and develop SRL as a possible targeted drug for cancer therapeutics.

ORGANISM(S): Homo sapiens

SUBMITTER: Nilanjan Guha 

PROVIDER: E-MTAB-3003 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress