Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells

Recent studies have shown that high insulin-like growth factor I (IGF-I) bl ood level is a risk factor in breast and prostate cancer. The aim of this s tudy was to determine whether the mitogenic activity of IGF-I in mammary ca ncer cells can be reduced by the dietary carotenoid lycopene. The anticance r activity of lycopene, the major tomato carotenoid, has been suggested by in vitro, in vivo, and epidemiological studies. Growth stimulation of MCF7 mammary cancer cells by IGF-I was markedly reduced by physiological concent rations of lycopene. The inhibitory effects of lycopene on MCF7 cell growth were not accompanied by apoptotic or necrotic cell death, as determined by annexin V binding to plasma membrane and propidium iodide staining of nucl ei in unfixed cells. Lycopene treatment markedly reduced the IGF-I stimulat ion of tyrosine phosphorylation of insulin receptor substrate I and binding capacity of the AP-1 transcription complex. These effects were not associa ted with changes in the number or affinity of IGF-I receptors, but with an increase in membrane-associated IGF-binding proteins, which were previously shown in different cancer cells to negatively regulate IGF-I receptor acti vation. The inhibitory effect of lycopene on IGF signaling was associated w ith suppression of IGF-stimulated cell cycle progression of serum-starved, synchronized cells. Moreover, in cells synchronized by mimosine treatment, lycopene delayed cell cycle progression after release from the mimosine blo ck. Collectively, the above data suggest that the inhibitory effects of lyc opene on MCF7 cell growth are not due to the toxicity of the carotenoid but , rather, to interference in IGF-I receptor signaling and cell cycle progre ssion.