Sensitization of estrogen receptor-positive breast cancer cell lines to 4-hydroxytamoxifen by isothiocyanates present in cruciferous plants
Pawlik A, Słomińska-Wojewódzka M, Herman-Antosiewicz A
European journal of nutrition · 39 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Funding not disclosed
Publication
- Published
- 2015-05-26 · Eur J Nutr · vol. 55 · issue 3 · pp. 1165–1180
- Publisher
- Springer Science+Business Media
- Cited
- 59 citations · more than 82% of similar papers · 1.6× the field average
- References
- 65 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Pharmacological Effects of Natural Compounds · Nitrogen and Sulfur Effects on Brassica
- Keywords
- Clonogenic assay, Estrogen receptor, Cancer research, Sulforaphane, Tamoxifen, Breast cancer, Viability assay, Survivin, Pharmacology, Cell growth, Cancer, Cruciferous vegetables, Chemistry, MCF-7, Apoptosis, Cancer cell, Medicine, Internal medicine, Biochemistry, Human breast
- MeSH
- cell line, tumor, humans, brassicaceae, breast neoplasms, sulfides, thiocyanates, tamoxifen, isothiocyanates, sulfoxides, receptors, estrogen, antineoplastic agents, phytogenic, apoptosis, cell proliferation, cell survival, down-regulation, gene expression regulation, neoplastic, drug resistance, neoplasm, bcl-2-associated x protein, inhibitor of apoptosis proteins, mcf-7 cells, perilipin-2, survivin
3 authors
From PL
- Anna PawlikUniversity of Gdańsk
- Monika Słomińska-WojewódzkaUniversity of Gdańsk
- Anna Herman-Antosiewicz · correspondingUniversity of Gdańsk
Abstract
Purpose
Tamoxifen has been used for the treatment of estrogen receptor (ER)-positive breast cancers and in women who are at an increased risk of breast cancer. Acquired resistance to this drug and its toxicity still pose a clinically significant problem, especially in the prevention setting. Isothiocyanates present in cruciferous plants, such as sulforaphane or erucin, have been shown to reduce growth of breast cancer cells in vivo and in vitro. In this study, we explored their ability to sensitize cancer cells to 4-hydroxytamoxifen.
Methods
We used three ER-positive breast cancer cell lines, T47D, MCF-7 and BT-474, as well as the drug-resistant T47D and MCF-7 derivatives. We examined the effect of 4-hydroxytamoxifen, isothiocyanates and their combinations on cell viability by MTT and clonogenic assays. Impact of treatments on the levels of proteins engaged in apoptosis and autophagy was determined by Western blotting.
Results
Isothiocyanates act in a synergistic way with 4-hydroxytamoxifen, and co-treatment reduces breast cancer cell viability and clonogenic potential more effectively than treatment with any single agent. This is connected with a drop in the Bcl-2/Bax ratio and the level of survivin as well as increased PARP cleavage, and elevation in ADRP, the mitochondrial stress marker. Moreover, isothiocyanates sensitize 4-hydroxytamoxifen-resistant T47D and MCF-7 cells to the drug.
Conclusion
Isothiocyanates enhance response to 4-hydroxytamoxifen, which allows for reduction of the effective drug concentration. Combinatorial strategy may hold promise in development of therapies and chemoprevention strategies against ER-positive breast tumors, even those with acquired resistance to the drug.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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