title: Cell cycle effects of L-sulforaphane, a major antioxidant from cruciferous vegetables: The role of the anaphase promoting complex.
abstract: L-sulforaphane (LSF) is a natural isothiocyanate found in cruciferous vegetables particularly broccoli. LSF has been identified as a potent antioxidant and anti-cancer agent and is widely known to regulate phase II detoxifying enzymes and induce cell cycle arrest or apoptosis in malignant cells in vitro and in vivo. Previous studies have found significant G2/M cell cycle arrest in response to LSF in various model of cancer and results have mainly been attributed to increased cyclin B1 protein levels and increased p21expression. Using genome-wide mRNA-Seq analysis we provide insights into the molecular mechanisms of action of LSF to identify a key pathway in cell cycle progression - the role of the anaphase promoting complex (APC) pathway. We evaluated gene expression changes in human erythroleukemic K562 cells following treatment with 15 μM LSF for 48h and compared them to immortalized human keratinocytes, human microvascular endothelial cells (HMEC-1) cells and normal human umbilical endothelial cells (HUVEC). We identified disparate gene expression changes in response to LSF between malignant and normal cells and immortalized cell lines. The results highlight significant down-regulation of kinase CDK1 which is suggestive that the existence and activity of APC/CDC20 complex will be inhibited along with its associated down-stream degradation of key cell cycle regulators preventing cell cycle progression from mitotic exit.
authors.affiliation: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 75 Commercial Road, Melbourne, Victoria, Australia. tom.karagiannis@bakeridi.edu.au.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Shelley
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.forename: Katherine
authors.initials: K
authors.lastname: Ververis
authors.forename: Tom C
authors.initials: TC
authors.lastname: Karagiannis