Phytoestrogens/Flavonoids Reverse Breast Cancer Resistance Protein/ABCG2-Mediated Multidrug Resistance

Imai, Yasuo; Tsukahara, Satomi; Asada, Sakiyo; Sugimoto, Yoshikazu

doi:10.1158/0008-5472.can-04-0078

Cited by 249 publications

(197 citation statements)

References 23 publications

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“…They also demonstrated that the mean BCRP protein level in the placenta was lower in homozygotes for the A421 allele than in those for the C421 allele and that heterozygotes had an intermediate level. 26 Although the molecular mechanism for the relationship between BCRP and carcinogenesis remains to be resolved, BCRP transports a wide variety of substances other than anticancer drugs, including fluorescent dyes, 27 sterols, 28 phytoestrogens, 29 chlorophyll derivatives 30 and folate. 31 Pheophorbide a, a chlorophyll derivative, was shown to have antimutagenic activity and to inhibit tumor cell growth.…”

Section: Discussionmentioning

confidence: 99%

Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma

Korenaga

Naito

Okayama

et al. 2005

Intl Journal of Cancer

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Breast cancer resistance protein (BCRP), the second member of the ATP-binding cassette membrane transporter family, has a single nucleotide polymorphism, C421A (resulting in Q141K), that is of functional importance. Our aim was to explore the relationship between this polymorphism of the BCRP gene and the risk of renal cell carcinoma (RCC) development. For a case-control study, DNA samples from 200 nonpapillary RCC patients and 200 healthy control subjects were analyzed using the TaqMan technique. The genotypic frequencies of the BCRP C421A polymorphism were compared between RCC patients and control subjects. The frequency of the C/C genotype was significantly higher in RCC patients than in control subjects (age-and gender-adjusted OR 5 1.96, 95% CI 1.32-2.93). No associations were observed between the BCRP C421A polymorphism and clinicopathologic or epidemiologic factors, including age, gender, tumor grade, stage, cigarette smoking, family history of cancer and body mass index. Carriers with the C/C genotype of the BCRP C421A polymorphism are at risk of developing nonpapillary RCC. These data suggest that BCRP is a candidate RCC susceptibility gene. ' 2005 Wiley-Liss, Inc.Key words: breast cancer resistance protein; single nucleotide polymorphism; renal cell carcinoma RCC is the most common malignancy of human adult kidneys and accounts for 2-3% of all cancers. Approximately 80% of all RCCs belong to the clear cell subtype, originating from the proximal epithelia.1 The prevalence of RCC is increasing, 2,3 probably for the following reasons: (i) an improved detection rate arising from the widespread use of noninvasive imaging procedures, such as ultrasonography, CT and MRI; (ii) prolongation of the life span in developed countries; and (iii) increases in environmental risk factors, especially exogenous carcinogens derived from various foods and industrial processes. Regarding the metabolism of such xenobiotics, genetically polymorphic enzymes such as cytochrome P-450, glutathione S-transferase and N-acetyltransferase have been reported to modulate renal cancer risk.4-6 Detection of high-risk groups based on the knowledge of cancer-susceptibility genes is clearly important for further improvement in the early diagnosis and prevention of RCC.Accumulating evidence has revealed that transporter molecules involved in the distribution, delivery and penetration of environmental agents into cellular and subcellular compartments may also play roles in the risk of renal cancer development.7,8 P-gp (MDR1/ABCB1), MRP2 (ABCC2) and BCRP (ABCG2) are members of the ABC transporter family, which function in the uptake, binding, transport and distribution of xenobiotics. P-gp is a plasma membrane transporter encoded by MDR1. Studies have shown that these proteins are expressed not only in cancer cells for effluxing multi-anticancer agents but also in the apical membrane of normal enterocytes, where they presumably act as ''gatekeepers'', controlling the oral availability of many substances. 9This hypothesis could be applicable t...

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Section: Discussionmentioning

confidence: 99%

Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma

Korenaga

Naito

Okayama

et al. 2005

Intl Journal of Cancer

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“…Pgp activity was shown to be inhibited by curcumin, ginsenosides, piperine, some cathechins from green tea, quercetin, and silymarin [14,29,30]. Genistein is a substrate of BCRP and therefore acts as a competitive inhibitor of BCRP-mediated transport [31].…”

Section: Mechanisms Of Cam-anticancer Drug Interactionsmentioning

confidence: 99%

Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction

2006

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An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment. Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb-anticancer drug interactions. Such a relevant interaction is that of St. John's wort with the anticancer drugs irinotecan and imatinib. It is, however, estimated that CAM-anticancer drug interactions are responsible for substantially more unexpected toxicities of chemotherapeutic drugs and possible undertreatment seen in cancer patients.Induction of drug-metabolizing enzymes and ATP-binding cassette drug transporters can be one of the mechanisms behind CAM-anticancer drug interactions. Induction will often lead to therapeutic failure because of lower plasma levels of the anticancer drugs, and will easily go unrecognized in cancer treatment, where therapeutic failure is common.Recently identified nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and the vitamin D-binding receptor, play an important role in the induction of metabolizing enzymes and drug transporters. This knowledge has already been an aid in the identification of some CAM probably capable of causing interactions with anticancer drugs: kavakava, vitamin E, quercetin, ginseng, garlic, β-carotene, and echinacea. Evidently, more research is necessary to prevent therapeutic failure and toxicity in cancer patients and to establish guidelines for CAM use. The Oncologist 2006;11:742-752 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the possible pharmacokinetic interactions between complementary alternative medicines and oncolytic drugs and the clinical consequences thereof.2. Define the role of the nuclear receptors PXR, CAR, and VDR in herb-drug interactions.3. Discuss methods to measure induction of drug-metabolizing enzymes and transporters.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit

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“…Many compounds have been shown to reverse BCRP-mediated drug resistance in vitro, including fumitremorgin C, an extract from Aspergillus fumigatus (20), GF120918, a compound developed as a P-glycoprotein inhibitor (21), estrogens like estrone and 17b-estradiol (22), novobiocin, a coumermycin antibiotic (23), and plant-derived hydroxyflavonoids such as genistein (24). Although BCRP inhibitors have been the subject of much investigation, relatively little research has been conducted in vivo on the reversing effects of BCRP inhibitors on drug resistance, and no inhibitor specifically targeting BCRP has been used in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo

Yamazaki

Nishiyama

Furuta

et al. 2011

Molecular Cancer Therapeutics

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Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38-resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1-mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

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Phytoestrogens/Flavonoids Reverse Breast Cancer Resistance Protein/ABCG2-Mediated Multidrug Resistance

Abstract: ABSTRACT

Cited by 249 publications

References 23 publications

Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma

Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma

Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction

Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo

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