Grape seed proanthocyanidin suppression of breast cell carcinogenesis induced by chronic exposure to combined 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone and benzo[a]pyrene
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Breast cancer is the most common type of cancer among women in northern America and northern Europe; dietary prevention is a cost‐efficient strategy to reduce the risk of this disease. To identify dietary components for the prevention of human breast cancer associated with long‐term exposure to environmental carcinogens, we studied the activity of grape seed proanthocyanidin extract (GSPE) in suppression of cellular carcinogenesis induced by repeated exposures to low doses of environmental carcinogens. We used combined carcinogens 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) and benzo[a]pyrene (B[a]P), at picomolar concentrations, to repeatedly treat noncancerous, human breast epithelial MCF10A cells to induce cellular acquisition of cancer‐related properties of reduced dependence on growth factors, anchorage‐independent growth, and acinar‐conformational disruption. Using these properties as biological target endpoints, we verified the ability of GSPE to suppress combined NNK‐ and B[a]P‐induced precancerous cellular carcinogenesis and identified the minimal, noncytotoxic concentration of GSPE required for suppressing precancerous cellular carcinogenesis. We also identified that hydroxysteroid‐11‐beta‐dehydrogenase 2 (HSD11B2) may play a role in NNK‐ and B[a]P‐induced precancerous cellular carcinogenesis, and its expression may act as a molecular target endpoint in GSPE's suppression of precancerous cellular carcinogenesis. And, the ability of GSPE to reduce gene expression of cytochrome‐P450 enzymes CYP1A1 and CYP1B1, which can bioactivate NNK and B[a]P, possibly contributes to the preventive mechanism for GSPE in suppression of precancerous cellular carcinogenesis. Our model system with biological and molecular target endpoints verified the value of GSPE for the prevention of human breast cell carcinogenesis induced by repeated exposures to low doses of multiple environmental carcinogens. © 2010 Wiley‐Liss, Inc.
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Previous research has demonstrated the inhibitory effect of proanthocyanidins on lipid metabolism and the expression of steroid metabolism-related enzymes, which can suppress breast cancer carcinogenesis.
“Previous research has demonstrated the inhibitory effect of PAs on lipid metabolism and the expression of steroid metabolism-related enzymes, which can suppress breast cancer carcinogenesis [30,31,32].”
From The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis (2023) · cites this paper as [32]
The Results (Molecular Target Endpoint for GSPE in Suppression of Carcinogenesis; page unavailable) report that grape seed proanthocyanidin extract reduced expression of HSD11B2, a steroid-metabolizing enzyme, in carcinogen-exposed breast cells. The Discussion reports suppression of precancerous cellular properties. The paper does not report inhibition of lipid metabolism, and its findings concern precancerous cells rather than demonstrated prevention of breast cancer. (LLM, conf=0.88)
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References 58 · Cited by 40
- Authors
- Song, X., Siriwardhana, N., Rathore, K., Lin, D., & Wang, H. R.
- Affiliations
- China Agricultural University (CN)
- University of Tennessee at Knoxville (US)
- Corresponding author
- Wang, Hwa‐Chain Robert
- Venue
- Molecular Carcinogenesis
- Publisher
- Wiley
- Published
- 2010-02-09
- Volume
- 49
- Issue
- 5
- Pages
- 450-463
- ISSN
- 0899-1987 (ISSN-L)
- 1098-2744
- PMC
- PMC3152701
- OpenAlex
- W2137179861
- Cited by
- 40
- References
- 58
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 8 · 2012: 6
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA125795, R03CA125795)
- Topics
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Keywords
- grape seed proanthocyanidins, breast cancer prevention, NNK, benzo[a]pyrene, MCF10A cells, anchorage-independent growth, 11β-hydroxysteroid dehydrogenase type 2, CYP1A1, CYP1B1, dietary chemoprevention, environmental carcinogens
- MeSH terms
- Base Sequence, Benzo(a)pyrene, Breast Neoplasms, Carcinogens, Cell Adhesion, Cell Transformation, Neoplastic, Female, Humans, Nitrosamines, Seeds, Blotting, Western, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Vitis, RNA Interference, Proanthocyanidins, Cell Line, Tumor
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