NDLI: Sensitization of estrogen receptor-positive breast cancer cell lines to 4-hydroxytamoxifen by isothiocyanates present in cruciferous plants

Content Provider	Springer Nature Link
Author	Pawlik, Anna Słomińska Wojewódzka, Monika Herman Antosiewicz, Anna
Copyright Year	2015
Abstract	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. 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.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.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.
Starting Page	1165
Ending Page	1180
Page Count	16
File Format	PDF
ISSN	14366207
Journal	European Journal of Nutrition
Volume Number	55
Issue Number	3
e-ISSN	14366215
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-05-27
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Breast cancer Sulforaphane Erucin 4-Hydroxytamoxifen Estrogen receptor Nutrition
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Medicine

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Sensitization of estrogen receptor-positive breast cancer cell lines to 4-hydroxytamoxifen by isothiocyanates present in cruciferous plants

Sensitization of estrogen receptor-positive breast cancer cell lines to 4-hydroxytamoxifen by isothiocyanates present in cruciferous plants

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