Prolonged Sulforaphane Treatment Activates Survival Signaling in Nontumorigenic NCM460 Colon Cells but Apoptotic Signaling in Tumorigenic HCT116 Colon Cells

摘要

Sulforaphane (SFN) is a naturally occurring chemopreventivenagent; the induction of cell cycle arrest and apoptosis is a keymech-nanism by which SFN exerts its colon cancer prevention. However,nlittle is known about the differential effects of SFN on colon can-ncer and normal cells. In this study, we demonstrated that SFNn(15 µmol/L) exposure (72 h) inhibited cell proliferation by upnto 95% in colon cancer cells (HCT116) and by 52% in normalncolon mucosa-derived (NCM460) cells. Our data also showed thatnSFN exposure (5 and 10 µmol/L) led to the reduction of G1 phasencell distribution and an induction of apoptosis in HCT116 cells,nbut to a much lesser extent in NCM460 cells. Furthermore, thenexamination of mitogen-activated protein kinase (MAPK) signal-ning status revealed that SFN upregulated the phosphorylation ofnextracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells butnnot in HCT116 cells. In contrast, SFN enhanced the phosphoryla-ntion of stress-activated protein kinase (SAPK) and decreased cellu-nlarmyelocytomatosis oncogene (c-Myc) expression inHCT116 cellsnbut not NCM460 cells. Taken together, the activation of survivalnsignaling in NCM460 cells and apoptotic signaling in HCT116 cellsnmay play a critical role in SFN’s stronger potential of inhibitingncell proliferation in colon cancer cells than in normal colon cells.