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

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.ResultsIsothiocyanates 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.ConclusionIsothiocyanates 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.

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

“…As a hydrophobic drug, TAM may induce oxidative stress due to the accumulation in phospholipid bilayers of membranes resulting in cell death at highest concentrations (Gundimeda et al, 1996). The effect of freeze-drying process on TAM biological activity was evaluated in vitro using MCF-7 cell line, an ER-positive breast cancer cell line (Pawlik et al, 2016). It was assessed the metabolic activity of cells after the incubation with different concentrations of TAM encapsulated into liposomes, before and after the freezedrying process.…”

Cisplatin combination drugs induce autophagy in HeLa cells and interact with HSA via electrostatic binding affinity

“…Simultaneously, various doses of RAPA in combination with 2 mg mL À1 cisplatin using HeLa cell lines resulted in a signicant synergistic antiproliferative effect, with a Combination Index (CI) of <1, at a range of 0.01 to 0.19 (ESI Table S1 †). [25][26][27][28][29][30] However, antagonism effects on cell proliferation were observed with a CI > 1 when different concentrations of RAPA were combined with higher concentration of cisplatin (40 mg mL À1 ) in HeLa cell lines (ESI Table S1 †). 25 HeLa cells exposed to different concentrations of cisplatin and RAPA have a time-dependent decrease of viability (Fig.…”

Mechanism of selective anticancer activity of isothiocyanates relies on differences in DNA damage repair between cancer and healthy cells

“…Nontumorigenic human mammary epithelial MCF-10A cells were resistant to SFNinduced oxidative stress and cell death [6]. Similarly, sulforaphene and erucin were much less potent towards MCF10A than a panel of breast cancer cell lines [7,8].…”