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

Michael Karas, Hadar Amir, Daniel Fishman, Michael Danilenko, Shraga Segal, Amit Nahum, Arie Koifmann, Yudit Giat, Joseph Levy, Yoav Sharoni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Recent studies have shown that high insulin-like growth factor I (IGF-I) blood level is a risk factor in breast and prostate cancer. The aim of this study was to determine whether the mitogenic activity of IGF-I in mammary cancer cells can be reduced by the dietary carotenoid lycopene. The anticancer 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 concentrations 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 nuclei in unfixed cells. Lycopene treatment markedly reduced the IGF-I stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and binding capacity of the AP-1 transcription complex. These effects were not associated 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 activation. The inhibitory effect of lycopene on IGF signaling was associated with 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 block. Collectively, the above data suggest that the inhibitory effects of lycopene 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 progression.

Original languageEnglish
Pages (from-to)101-111
Number of pages11
JournalNutrition and Cancer
Issue number1
StatePublished - 2000
Externally publishedYes


FundersFunder number
Israel Ministry of Health
S. Daniel Abraham International Center for Health and Nutrition
Israel Academy of Sciences and Humanities
Israel Cancer Association
Israel Science Foundation
Ben-Gurion University of the Negev


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