Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2010
Publication Date: 2/1/2011
Publication URL: http://handle.nal.usda.gov/10113/58089
Citation: Zeng, H., Trujillo, O.N., Moyer, M.P., Botnen, J.H. 2011. Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells. Nutrition and Cancer. 63(2):248-255. Interpretive Summary: Sulforaphane is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which sulforaphane exerts its colon cancer prevention. Although there are no precise data on achievable sulforaphane concentrations in human colon, previous studies have estimated that 100g of broccoli could yield up to 40 u mol of sulforaphane. However, little is known about the differential effects of sulforaphane on colon cancer cells and normal cells. In this study, we demonstrated that prolonged sulforaphane treatment inhibits cell growth, and induces cell cycle arrest, apoptosis in colon cancer cells, but to a lesser extent in nontumorigenic cells. Thus, the elucidation of the mechanisms by which sulforaphane regulates the cell cycle and apoptosis can lead to a better understanding of the nature of sulforaphane’s anticancer activity. The information will be useful for scientists and health-care professionals who are interested in nutrition and cancer prevention.
Technical Abstract: Sulforaphane (SFN) is a naturally occurring member of the isothiocyanate family of chemopreventive agents and the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (5, 10 or 15 u mol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure led to the significant induction of apoptosis and G2/M cell cycle arrest in HCT116, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that prolonged SFN treatment strongly up-regulated the phosphorylation of extracellular-regulated kinase ½ (ERK1/2) in NCM460 but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased c-Myc expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 and apoptotic signaling in HCT116 cells may play a critical role in SFN’s stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells.