Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy

Noguchi, Kohji; Katayama, Kazuhiro; Mitsuhashi, Junko; Sugimoto, Yoshikazu

doi:10.1016/j.addr.2008.07.003

Cited by 119 publications

(84 citation statements)

References 107 publications

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“…Two examples of such interaction are given next. First, BCRP acts as an efflux transporter for various anticancer agents including 5-fluorouracil, methotrexate, mitoxantrone, anthracyclines, daunorubicin, doxorubicin, topotecan, diflomotecan, irinotecan, tyrosine kinase inhibitors (e.g., imatinib and gefitinib), and nucleoside analogs (49,52). Thus it prevents the buildup of high intracellular concentrations of such anticancer agents and decreases their cytotoxic effects.…”

Section: Discussionmentioning

confidence: 99%

The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

Gonçalves

Gregório

Martel

2011

American Journal of Physiology-Cell Physiology

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Gonçalves P, Gregório I, Martel F. The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein. Am J Physiol Cell Physiol 301: C984 -C994, 2011. First published July 20, 2011 doi:10.1152/ajpcell.00146.2011.-Colorectal cancer is one of the most common cancers worldwide. Butyrate (BT) plays a key role in colonic epithelium homeostasis. The aim of this work was to investigate the possibility of BT being transported by P-glycoprotein (MDR1), multidrug resistance proteins (MRPs), or breast cancer resistance protein (BCRP). Uptake and efflux of 14 C-BT and 3 H-folic acid were measured in Caco-2, IEC-6, and MDA-MB-231 cell lines. mRNA expression of BCRP was detected by RT-PCR. Cell viability, proliferation, and differentiation were quantified with the lactate dehydrogenase, sulforhodamine B, and alkaline phosphatase activity assays, respectively. In both IEC-6 cells and Caco-2 cells, no evidence was found for the involvement of either MDR1 or MRPs in 14 C-BT efflux from the cells. In contrast, several lines of evidence support the conclusion that BT is a substrate of both rat and human BCRP. Indeed, BCRP inhibitors reduced 14 C-BT efflux in IEC-6 cells, both BT and BCRP inhibitors significantly decreased the efflux of the known BCRP substrate 3 H-folic acid in IEC-6 cells, and BCRP inhibitors reduced 14 C-BT efflux in the BCRP-expressing MDA-MB-231 cell line. In IEC-6 cells, combination of BT with a BCRP inhibitor significantly potentiated the effect of BT on cell proliferation. The results of this study, showing for the first time that BT is a BCRP substrate, are very important in the context of the high levels of BCRP expression in the human colon and the anticarcinogenic and anti-inflammatory role of BT at that level. So, interaction of BT with BCRP and with other BCRP substrates/inhibitors is clearly of major importance. butyrate efflux; colorectal cancer; IEC-6 cells; anticarcinogenic effect COLORECTAL CANCER (CRC) is a leading cause of cancer death in occidental countries (36). Butyrate (BT), a product of intestinal flora fermentation of dietary fiber, has a protective role in the prevention and progression of colorectal carcinogenesis (57). Indeed, this short-chain fatty acid plays a key role in colonic epithelium homeostasis, by having multiple important roles at that level: 1) it is the main energy source for colonocytes, 2) it promotes growth and proliferation of normal colonic epithelial cells, 3) it inhibits colon carcinogenesis (by suppressing growth of cancer cells, inducing differentiation and apoptosis and inhibiting cell proliferation), 4) it inhibits colon inflammation and oxidative stress, 5) it improves the colonic defence barrier function, and 6) it stimulates fluid and electrolyte absorption (reviews in Refs. 31, 68). 1The mechanism by which BT inhibits colon carcinogenesis seems to involve various effects on gene expression, which are mainly attributed to its capacity to act as a histone deacetylase inhibitor (HDAC), leading to hyperacetylation of histones and to incr...

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Section: Discussionmentioning

confidence: 99%

The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

Gonçalves

Gregório

Martel

2011

American Journal of Physiology-Cell Physiology

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“…The protein, which belongs to the ABCG subfamily of ABC transporters, is an inverted halftransporter composed of an N-terminal nucleotide-binding site and a carboxyterminal transmembrane domain, which contains six membrane spanning helices (Gottesman et al, 2002;Gradhand & Kim, 2008). In its functional form, it is homodimeric and widely expressed in human tissues (Noguchi et al, 2009). Similar to ABCB1 and ABCC1 it plays an important role in intercellular drug absorption, distribution, metabolism, and excretion, as well as toxicity.…”

Section: Breast Cancer Resistance Proteinmentioning

confidence: 99%

Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer

et al. 2016

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Breast cancer is a serious threat to women's health, because multidrug resistance (MDR) has hampered treatment and prognosis. Nanodelivery of anticancer agents is a new technology to be exploited in the treatment of patients, because it bypasses multispecific drug efflux transporters such as P-glycoprotein (ABCB1), multidrug resistance protein-1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). Drugs can be delivered to tumor tissue by passive and active tumor targeting strategies, which may reduce or reverse drug resistance. This review will mainly focus on MDR-associated proteins, as well as various nanoparticle formulations developed to overcome MDR in breast cancer.

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“…Expression of BCRP can thus confer a multidrug resistance phenotype on cancer cells. 10) BCRP is highly expressed in placental syncytiotrophoblasts, in the apical membrane of the epithelium in the small intestine, in the liver canalicular membrane, and at the luminal surface of the endothelial cells of human brain microvessels. 11) This strategic and abundant tissue localization indicates that BCRP plays an important role in absorption, distribution, and elimination of drugs and environmental chemicals that are BCRP substrates, such as antibiotics, topotecan, and dietary carcinogens.…”

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confidence: 99%