Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

Choi, Hoo Kyun; Yang, Jin Won; Roh, Sang Hee; Han, Chang Yeob; Kang, Keon Wook

doi:10.1677/erc-06-0016

Cited by 79 publications

(96 citation statements)

References 34 publications

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“…Genistein glucuronides and sulfates have poor lipid solubility and carry net negative charges at physiological pH levels, so they must transverse the cell membrane (into the cells) by a carrier-mediated transport before they can react with the hydrolytic enzymes inside the cells. Efflux transporters existed in breast cells, such as MRP2 and BCRP (37,38), limit their presence in cells by excreting them rapidly (39)(40)(41), all of which could lead to weak hydrolytic metabolism. Hence, transporters mediating the influx or efflux of genistein conjugates probably play an important role in the metabolism of genistein conjugates in breast cells, and further studies are underway to define these transporters.…”

Section: Discussionmentioning

confidence: 99%

Role of Metabolism in the Effects of Genistein and Its Phase II Conjugates on the Growth of Human Breast Cell Lines

Yuan

Wang

Jin

et al. 2012

AAPS J

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Abstract. Genistein has been investigated for several decades for its potential role in breast cancer prevention. Previous researches have shown that glucuronide and sulfate conjugates are the major species circulating in the blood after genistein ingestion. It was hypothesized that enzymes (UDPglucuronosyltransferases, sulphotransferases, β-glucuronidases, and sulphatases) present in breast tissues would catalyze the inter-conversion between the aglycone and the conjugates in situ. Therefore, our aim was to investigate how genistein, genistein-7-glucuronide (G-7-G), genistein-7-sulfate (G-7-S), and 4′-sulfate (G-4′-S) were metabolized in mammary cells and to determine the effects of metabolism on their proliferative actions using cultured breast cell lines. As expected, genistein stimulated the cell growth of breast cancer cells (MCF-7 and T47D) concentration-dependently at lower concentrations but inhibited their growth at higher concentration. It showed low activities in a non-tumorigenic cell line (MCF-10A) due to the absence of ERα. Genistein was extensively metabolized to glucuronides by MCF-7 and to sulfates by T47D, while it was poorly metabolized by MCF-10A. G-7-G displayed weak stimulation activity in breast cancer cells. G-7-G underwent extensive metabolism in T47D and MCF-10A but not in MCF-7. The proliferative effects of G-7-G on MCF-7 and T47D were associated with its hydrolysis to genistein in these cells. In contrast, G-7-S and G-4′-S were not metabolized by these three cells and had no effects on their growth. In conclusion, production of phase II metabolites did not affect the proliferation effect of genistein on MCF-7 and T47D. Deconjugation was correlated to the apparent proliferative effects of G-7-G in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Role of Metabolism in the Effects of Genistein and Its Phase II Conjugates on the Growth of Human Breast Cell Lines

Yuan

Wang

Jin

et al. 2012

AAPS J

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“…Initially, cell growth rates were reduced. However, after exposure to the medium for 9 mo, the rate of cell growth gradually increased with the establishment of a TAM-resistant cell line (5).…”

Section: Methodsmentioning

confidence: 99%

“…Although most patients are initially responsive, resistance to TAM develops, which is a critical problem for antiestrogen therapy (4). To mimic this condition, an MCF-7-derived TAM-resistant cell line (TAMR-MCF-7 cells) was established by long-term (>9 months) culture of MCF-7 cells with 4-hydroxytamoxifen (5,6).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of vascular endothelial growth factor–mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression

Kim

Choi

Yang

et al. 2009

Molecular Cancer Therapeutics

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“…Initially, the cell growth rates were reduced. However, after exposure to the medium for 9 months, the rate of cell growth gradually increased, showing the establishment of a tamoxifen-resistant cell line [30].…”

Section: Cell Culturementioning

confidence: 99%

Combination of siRNA-directed gene silencing with epigallocatechin-3-gallate (EGCG) reverses drug resistance in human breast cancer cells

Esmaeili

2015

J Chem Biol

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Elevated expression of NF-E2-related factor 2 (Nrf2), a nuclear transcription factor, is a frequent genetic abnormality seen in this malignancy and is an important contributor to chemoresistance in cancer therapy. In the present study, we investigated if Nrf2 was associated with drug resistance in tamoxifen-resistant MCF-7 (MCF-7/TAM) cells, and whether EGCG, major flavonoid isolated from green tea, could reverse drug resistance in MCF-7/TAM cells. Our results showed that the endogenous expression of Nrf2 as well as its target proteins heme oxygenase-1, NADP (H):quinone oxidoreductase in MCF-7/TAM cells was higher than that in MCF-7 cells. Epicatechin gallate (EGCG) significantly sensitizes MCF-7/TAM cells to tamoxifen and dramatically reduced Nrf2 expression at both the messenger RNA and protein, leading to a reduction of Nrf2-downstream genes. In addition, using siRNA technique, we found that the intracellular Nrf2 protein level was significantly decreased in MCF-7/ TAM cells and tamoxifen resistance was partially reversed by Nrf2 siRNA. Combination of siRNA-directed gene silencing with EGCG downregulated the Nrf2-dependent response and partly reversed tamoxifen resistance in MCF-7/TAM cells in a synergic manner. These results suggested that combining the chemotherapeutic effect of EGCG with siRNA-mediated Nrf2 knock-down results in the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs.

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Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

Cited by 79 publications

References 34 publications

Role of Metabolism in the Effects of Genistein and Its Phase II Conjugates on the Growth of Human Breast Cell Lines

Role of Metabolism in the Effects of Genistein and Its Phase II Conjugates on the Growth of Human Breast Cell Lines

Enhancement of vascular endothelial growth factor–mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression

Combination of siRNA-directed gene silencing with epigallocatechin-3-gallate (EGCG) reverses drug resistance in human breast cancer cells

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