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Title: IBERIN INDUCES CELL CYCLE ARREST AND APOPTOSIS IN HUMAN NEUROBLASTOMA CELLS

Author
item JADHAV, UNMESH - UNIVERSITY OF ILLINOIS
item EZHILARASAN, RAVESANKER - UNIVERSITY OF ILLINOIS
item Vaughn, Steven
item Berhow, Mark
item MOHANAM, SANJEEVA - UNIVERSITY OF ILLINOIS

Submitted to: Trade Journal Publication
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/2/2007
Publication Date: 3/16/2007
Citation: Jadhav, U., Ezhilarasan, R., Vaughn, S.F., Berhow, M.A., Mohanam, S. 2007. Iberin induces cell cycle arrest and apoptosis in human neuroblastoma cells. International Journal of Molecular Medicine 19(3):353-361.

Interpretive Summary: The National Cancer Institute estimates that about one-third of all cancers are linked to diet. Consumption of certain foods has been associated with lowering cancer incidence, including brain tumors. Cruciferous vegetables, such as cabbage, broccoli, and cauliflower, contain a group of chemicals called glucosinolates which degrade to form potent anti-cancer compounds. One of these degradation compounds, called iberin, was found to inhibit the growth of human cancer cells. These findings indicate that iberin functions by inducing cell arrest and cell death in cultured human nerve cancer cells, and has a strong potential for use as a therapeutic agent against cancer.

Technical Abstract: Epidemiological studies have indicated that increased consumption of cruciferous vegetables is associated with a statistically significant reduction in the risk for cancers. The major bioactive agent in these vegetables is a class of sulfur-containing glycosides called glucosinolates. Isothiocyanates, derivatives of glucosinolates, have been shown to possess anticancer properties in a variety of tumor cell lines. In this study, we evaluated the antigrowth, cell cycle modulation and proapoptotic effects of isothiocyanate iberin in human neuroblastoma cells. Treatment of neuroblastoma cells with iberin resulted in a dose- and time-dependent inhibition of growth, increased cytotoxicity, and G1 or G2 cell cycle arrest depending upon cell type. The iberin-induced cell cycle arrest in neuroblastoma cells was associated with inhibition of expression of Cdk2, Cdk4 and Cdk6 proteins. Fluorescence microscopic analysis of DNA-staining patterns with DAPI revealed an increase in apoptotic cell death in iberin-treated cells as compared with control cells. FLICA staining showed that iberin induced apoptosis, and this apoptotic induction was found to be associated with the activation of caspase-9, caspase-3 and PARP. These findings suggest that the anticancer efficacy of iberin is mediated via induction of cell cycle arrest and apoptosis in human neuroblastoma cells, and has strong potential for development as a therapeutic agent against cancer.