Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1
Abstract
Background Insulin-like growth factors (IGFs) play an important role in normal and cancerous cell proliferation. Moreover, in recent studies IGF-I has been implicated as a major cancer risk factor. The tomato carotenoid lycopene and all-trans retinoic acid (atRA) have been shown to inhibit growth factor-induced proliferation of different types of cancer cells. This action is associated with inhibition of cell cycle progression in G0/G1 phase. Cyclin D1 acts as a growth factor sensor in G1 phase and is overexpressed in many breast cancer tumors. We have previously demonstrated that slowdown of serum-stimulated cell cycle progression from G1 to S phase by lycopene correlates with reduction in cyclin D1 levels, suggesting that the expression of this protein is a main target for lycopene's action.Aim of the study To determine whether the reported reduction in cyclin D1 level is the key mechanism for lycopene and atRA inhibitory action on IGF-I-induced cell cycle progression.Results Human breast (MCF-7) and endometrial (ECC-1) cancer cells were synchronized in G0/G1 phase by serum deprivation followed by stimulation with IGF-I. Cell treatment with lycopene and atRA inhibited IGF-I-stimulated cell cycle progression from G1 to S phase and decreased retinoblastoma protein (pRb) phosphorylation. These events were associated with a reduction in cyclin D1 and p21(CIP1/WAF1) level, but not that of p27(KIP1). To test the hypothesis that the decrease in cyclin D1 has a major role in the inhibitory effects of lycopene and atRA, we examined the ability of these two agents to suppress cell cycle progression in MCF-7.7D1.13 cells which are capable of expressing cyclin D1 under the control of the Zn-inducible metallothionein promoter. Our results showed that ectopic expression of cyclin D1 can overcome cell cycle inhibition caused by lycopene and atRA.Conclusions Our findings suggest that attenuation of cyclin Dl levels by lycopene and atRA is an important mechanism for the reduction of the mitogenic action of IGF-I.
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Growth inhibition of lycopene on MCF-7 breast cancer cells is associated with decreased G1-S cell cycle progression, decreased cyclin D1 expression, and stabilization of p27 in the cyclin E-CDK complex.
“It has been reported that the growth inhibition of lycopene on MCF-7 breast cancer cells was also associated with decreased G1-S cell cycle progression, decreased cyclin D1 expression, and stabilization of p27 in the cyclin E-CDK complex [7, 66].”
From The Effect of Lycopene Preexposure on UV‐B‐Irradiated Human Keratinocytes (2016) · cites this paper as [66]
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- Authors
- Nahum, A., Zeller, L., Danilenko, M., Prall, O. W. J., Watts, C. K. W., Sutherland, R. L., Levy, J., & Sharoni, Y.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Levy, Joseph
- Venue
- European Journal of Nutrition
- Published
- 2006-03-24
- Volume
- 45
- Issue
- 5
- Pages
- 275-282
- ISSN
- 1436-6207 (ISSN-L)
- 1436-6215
- OpenAlex
- W1969071751
- Cited by
- 99
- References
- 33
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Academy of Sciences and Humanities
- Israel Science Foundation
- Division of Electrical, Communications and Cyber Systems
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- lycopene, insulin-like growth factor I, cyclin D1, all-trans retinoic acid, cell cycle progression, G1/S transition, retinoblastoma protein phosphorylation, p21, breast cancer cells, endometrial cancer cells, tomato carotenoids, cancer cell proliferation inhibition
- MeSH terms
- Lycopene, Antineoplastic Agents, Breast Neoplasms, Carotenoids, Cell Cycle, Cell Division, Female, Humans, Insulin-Like Growth Factor I, Phosphorylation, Time Factors, Tretinoin, Tumor Cells, Cultured, Blotting, Western, Endometrial Neoplasms, Culture Media, Serum-Free, Cyclin D1
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