Submitted to: American Association of Cancer Research Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/20/2005
Publication Date: 4/20/2005
Citation: Jadhav, U., Vaughn, S.F., Berhow, M.A., Rao, J.S., Mohanam, S. 2005. Studies on the mechanism of the inhibition of human neuroblastoma tumor cell growth by dietary isothiocyanate iberin in vitro [abstract]. American Association of Cancer Research Meeting. p. 3075.
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, which are degraded enzymatically or nonenzymatically to thiocyanates, isothiocyanates and nitriles. Isothiocyantes, such as sulforaphane, have been shown to inhibit cell proliferation and induce apoptosis in colon and prostate cancer cells. However, the antitumor properties of isothiocyanate iberin remain much less understood. In this study, we evaluated the antigrowth and proapoptotic effects of isothiocyante iberin in human neuroblastoma cells. The viability of cells was evaluated by MTT assay, and cytotoxicity was assayed by lactate dehydrogenase (LDH) released into the culture medium. Our results demonstrated that iberin suppresses proliferation and increases cytotoxicity in neuroblastoma cells. To explore the cell cycle effects of iberin, neuroblastoma cells were exposed to different concentrations and analyzed by flow cytometry after propidium iodide staining. The G1 phase population in these experiments increased whereas the G2-M population decreased when compared with vehicle control. 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. Fluorochrome caspase inhibitor staining showed that iberin-caused apoptosis is associated with activation of caspases. Further, we observed that caspase cascade is the major pathway activated by iberin through analysis of different caspase levels. These findings suggest that the novel anticancer efficacy of iberin mediated growth arrest and apoptosis in human neuroblastoma cells may have potential therapeutic use and warrant further in vivo investigation.