研究者詳細 - 中村　宜督

論文 - 中村　宜督

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第65回大会特別講演ポリフェノールの機能性の分子メカニズム : ポリフェノールはどのようにして機能性を発揮するのか—Molecular mechanisms for polyphenol functionality : How do polyphenols exert their functionality? 招待査読

中村宜督

日本食生活学会誌 = Journal for the integrated study of dietary habits / 日本食生活学会編 33 ( 4 ) 165 - 169 2023年

Construction of benzyl isothiocyanate-loaded fish skin gelatin-luteolin compound emulsion delivery system, and its digestion and absorption characteristics. 査読国際誌

Zhiyu Liu, Songyi Lin, Wenwen Liu, Yoshimasa Nakamura, Yue Tang

Journal of the science of food and agriculture 103 ( 4 ) 1864 - 1873 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Fish skin gelatin (FSG) and luteolin (LUT) were used as composite emulsifiers, and benzyl isothiocyanate (BITC) was used as a model of nutrient delivery to construct a stable emulsion. The storage stability of the FSG-LUT emulsion and its effect on BITC release were investigated both in vitro and ex vivo. RESULTS: LUT can quench FSG fluorophores statically and form a stable complex through hydrogen bonding and hydrophobic interactions. The FSG-LUT emulsion storage stability and embedding rate were higher than those of the FSG emulsion. The FSG-LUT emulsion microstructure was resistant to oral and gastric digestion, and the BITC retention rate and bioaccessibility were much higher than those of the FSG emulsion. Lastly, the ex-vivo everted gut sac of rat intestine study demonstrated that BITC showed the highest absorption in the ileum, and the FSG-LUT emulsion absorbed BITC and sustained a controlled release in a specific position. CONCLUSION: LUT could form stable complexes with FSG, which improved the stability and bioavailability of BITC in the FSG-LUT emulsion delivery system, and promoted further intestinal BITC absorption. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jsfa.12411

Phlorotannin Extracts from Ascophyllum nodosum Inhibited Proteases Activities and Structural Changes from Apostichopus japonicus 査読

Yu Ming, Yingzhen Wang, Yuqianqian Xie, Chenghang Sun, Xiufang Dong, Yoshimasa Nakamura, Xing Chen, Xiuping Dong, Hang Qi

ACS Food Science & Technology 2 ( 10 ) 1586 - 1596 2022年10月

Effects of Domestic Cooking Methods on Physichochemical Properties, Bioactive Compounds and Antioxidant Activities of Vegetables: A Mini-Review 査読

Shan Jiang, Meiqi Yu, Pengfei Jiang, Yoshimasa Nakamura, Hang Qi

Food Reviews International 1 - 15 2022年10月

Immune State Conversion of the Mesenteric Lymph Node in a Mouse Breast Cancer Model. 査読国際誌

Tsukasa Shigehiro, Maho Ueno, Mayumi Kijihira, Ryotaro Takahashi, Chiho Umemura, Eman A Taha, Chisaki Kurosaka, Megumi Asayama, Hiroshi Murakami, Ayano Satoh, Yoshimasa Nakamura, Junichiro Futami, Junko Masuda

International journal of molecular sciences 23 ( 19 ) 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-γ production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-γ expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103+CD11b+ dendritic cells (DCs) into the mLN, along with increased (1→3)-β-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103+CD11b+ DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.

DOI： 10.3390/ijms231911035

Extracellular malate induces stomatal closure via direct activation of guard-cell anion channel SLAC1 and stimulation of Ca2+ signaling. 査読国際誌

Yoshiharu Mimata, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

The New phytologist 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Plants secrete malate from guard cells to apoplast under stress conditions and exogenous malate induces stomatal closure. Malate is considered as an extracellular chemical signal of stomatal closure. However, the molecular mechanism of malate-induced stomatal closure is not fully elucidated. We investigated responses of stomatal aperture, ion channels, and cytosolic Ca2+ to malate. A treatment with malate induced stomatal closure in Arabidopsis thaliana wild-type plants but not in the mutants deficient in the slow (S-type) anion channel gene SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1). The treatment with malate increased S-type anion currents in guard-cell protoplasts of wild-type plants but not in the slac1 mutant. In addition, extracellular rather than intracellular application of malate increased the S-type currents of constitutively active mutants of SLAC1, which have kinase-independent activities, in a heterologous expression system using Xenopus oocytes. The treatment with malate transiently increased cytosolic Ca2+ concentration in the wild-type Arabidopsis guard cells and the malate-induced stomatal closure was inhibited by the Ca2+ channel blocker and the Ca2+ chelator. These results indicate that extracellular malate directly activates SLAC1 and simultaneously stimulates Ca2+ signaling in guard cells, resulting in steady and solid activation of SLAC1 for stomatal closure.

DOI： 10.1111/nph.18400

Negative regulation of salicylic acid-induced stomatal closure by glutathione in Arabidopsis thaliana. 査読国際誌

Fahmida Akter, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

Bioscience, biotechnology, and biochemistry 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Salicylic acid (SA) is a ubiquitous phenolic phytohormone that induces stomatal closure. Glutathione (GSH) negatively regulates stomatal closure induced by other plant hormones such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, the involvement of GSH in SA-induced stomatal closure is still unknown. We investigated the regulation of SA signaling by GSH in guard cells using an Arabidopsis thaliana mutant, cad2-1, which is deficient in the first GSH biosynthesis enzyme, γ-glutamylcysteine synthetase. Application of SA decreased stomatal apertures with decreasing intracellular GSH level in guard cells. Decreasing GSH by the cad2-1 mutation and by a GSH-decreasing chemical, 1-chloro-2,4-dinitrobenzene, enhanced the SA-induced stomatal closure. A treatment with glutathione monoethyl ester restored the GSH level in the cad2-1 guard cells and complemented the stomatal phenotype of the mutant. These results indicate that GSH negatively modulates SA-induced stomatal closure in A. thaliana.

DOI： 10.1093/bbb/zbac116

Malate induces stomatal closure via a receptor-like kinase GHR1- and reactive oxygen species-dependent pathway in Arabidopsis thaliana. 査読国際誌

Yoshiharu Mimata, Shintaro Munemasa, Fahmida Akter, Israt Jahan, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

Bioscience, biotechnology, and biochemistry 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

A primary metabolite malate is secreted from guard cells in response to the phytohormone abscisic acid (ABA) and elevated CO2. The secreted malate subsequently facilitates stomatal closure in plants. Here, we investigated the molecular mechanism of malate-induced stomatal closure using inhibitors and ABA signaling component mutants of Arabidopsis thaliana. Malate-induced stomatal closure was impaired by a protein kinase inhibitor, K252a, and also by the disruption of a receptor-like kinase GHR1, which mediates activation of calcium ion (Ca2+) channel by reactive oxygen species (ROS) in guard cells. Malate induced ROS production in guard cells while the malate-induced stomatal closure was impaired by a peroxidase inhibitor, salicylhydroxamic acid, but not by the disruption of NAD(P)H oxidases, RBOHD and RBOHF. The malate-induced stomatal closure was impaired by Ca2+ channel blockers, verapamil and niflumic acid. These results demonstrate that the malate signaling is mediated by GHR1 and ROS in Arabidopsis guard cells.

DOI： 10.1093/bbb/zbac122

Modulating effects of oral administration of Lycii Fructus extracts on UVB-induced skin erythema: A Randomized, placebo-controlled study. 査読国際誌

Makoto Tsunenaga, Wensi Xu, Takumi Myojin, Toshiyuki Nakamura, Tatsuya Kon, Yoshimasa Nakamura, Osamu Ueda

Biomedical reports 17 ( 1 ) 62 - 62 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Severe UV exposure induces skin inflammation, causing erythema. Lycii Fructus (Lycium barbarum and Lycium chinense) is a potential antioxidant agent with a high content of polyphenols, including rutin and chlorogenic acid. This study examined the effects of Lycii Fructus extract (LFE) on UVB-induced skin erythema in humans. Healthy volunteers were randomly assigned to one of two groups and received UVB irradiation at 1.5 minimal erythemal dose (MED) on day 0 at three designated sites on their backs, and the skin color was measured until day 7. After an 8-week treatment with LFE (900 mg/day) or placebo, UVB irradiation (l.5 MED) was applied again at different sites on day 63. Skin color was continuously measured in each group until day 69. LFE tablet administration for 8 weeks significantly inhibited UVB-induced erythema formation and increased the MED by 13%. Erythema formation peaked on the first day after UVB irradiation, but gradually dissipated over the next several days. LFE tended to accelerate erythema disappearance. To determine the polyphenol responsible for the protection against UVB-induced skin damage, the effects of LFE-derived polyphenols and their metabolites on UVB-induced cytotoxicity were examined in vitro. The major intestinal metabolite of rutin and LFE significantly attenuated phototoxicity and in human keratinocyte HaCaT cells. Quercetin enhanced intracellular glutathione levels in HaCaT cells, even though LFE did not increase it. Together, the results showed that LFE inhibited erythema formation and accelerated erythema dissipation, possibly through its direct antioxidative action.

DOI： 10.3892/br.2022.1545

過熱水蒸気処理玄米の食味,物性および抗酸化活性の評価—Evaluation of sensory properties, physical characteristics and antioxidant activity of superheated steam-treated brown rice 査読

西本有紀, 矢野愛奈, Wu Hongyan, 西澤正人, 中村俊之, 藤田明子, 中村宜督

美味技術学会誌 = Journal of the Japanese Society of Taste Technology 21 ( 1 ) 20 - 26 2022年7月

Antioxidative Effect of Chlorella Pyrenoidosa Protein Hydrolysates and Their Application in Krill Oil-in-Water Emulsions. 査読国際誌

Yujia Liu, Yuli Qi, Qi Wang, Fawen Yin, Honglei Zhan, Han Wang, Bingnan Liu, Yoshimasa Nakamura, Jihui Wang

Marine drugs 20 ( 6 ) 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Chlorella pyrenoidosa is an excellent source of protein, and in this research, we assessed the antioxidant and emulsifying effects of Chlorella protein hydrolysate (CPH) using neutral proteases and alkaline proteases, as well as the properties of CPH-derived krill oil-in-water (O/W) emulsions. The CPHs exhibited the ability to scavenge several kinds of free radicals, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), O2-, hydroxyl, and ABTS. Additionally, the CPHs (5 mg/mL) scavenged approximately 100% of the DPPH and ABTS. The CPHs showed similar emulsifying activities to Tween 20 and excellent foaming activities (max FS 74%), which helped to stabilize the krill oil-in-water emulsion. Less than 10 mg/mL CPHs was able to form fresh krill oil-in-water emulsions; moreover, the CPHs (5 mg/mL) in a krill O/W emulsion were homogenous, opaque, and stable for at least 30 days. Based on their inhibitory effects on the peroxide value (POV) and thiobarbituric acid reactive substances (TRABS), the CPHs were found to be able to inhibit lipid oxidation in both emulsifying systems and krill O/W emulsions. Thus, the CPHs could improve superoxide dismutase (SOD) activities by 5- or 10-fold and decrease the high reactive oxygen species (ROS) level caused by the addition of H2O2 in vitro. In conclusion, health-promoting CPHs could be applied in krill oil-in-water emulsions as both emulsifiers and antioxidants, which could help to improve the oxidative and physical stability of emulsions.

DOI： 10.3390/md20060345

Influence of fish skin gelatin-sodium alginate complex stabilized emulsion on benzyl isothiocyanate stability and digestibility in vitro and in vivo. 査読国際誌

Xiangyu Zhang, Zhiyu Liu, Ailin Wang, Simin Zhang, Yoshimasa Nakamura, Songyi Lin, Yue Tang

Journal of the science of food and agriculture 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: An emulsion delivery system for benzyl isothiocyanate (BITC) was prepared using fish skin gelatin (FSG) and sodium alginate (Alg). The effects of the FSG-Alg complex on the emulsion stability and BITC release pattern from the emulsion were investigated in vitro and in vivo. RESULTS: The storage stability and embedding rate of the 10 g/kg FSG and 2.5 g/kg Alg (FSG-Alg) emulsion were the highest among all samples. The FSG-Alg complex provided BITC a better protection during in vitro digestion. The microstructure of the FSG-Alg emulsions was more stable during in vitro digestion, and the bioaccessibility and retention rate of BITC were much higher compared to those of the FSG emulsion. The results of the ex-vivo everted gut sac of rat intestine study showed that the FSG-Alg emulsion significantly increased the BITC absorption rate in the duodenum. CONCLUSION: The FSG-Alg emulsion delivery system is a highly stable system for the delivery of BITC that improves the bioaccessibility of BITC and promotes its absorption in the duodenum. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jsfa.11915

RING FISSION CATABOLITES OF QUERCETIN GLYCOSIDES

LI Kexin, NAKAMURA Toshiyuki, NAKAMURA Yoshimasa

Journal of Environmental Science for Sustainable Society 11 ( Supplement ) MR02_p5 - MR02_p8 2022年4月

Characterization of a synthetic zinc-chelating peptide from sea cucumber (Stichopus japonicus) and its gastrointestinal digestion and absorption in vitro. 査読国際誌

Zixu Wang, Jiatong Sun, Xiaoyu Ma, Xiaoyang Liu, Fawen Yin, Deyang Li, Yoshimasa Nakamura, Chenxu Yu, Dayong Zhou

Journal of the science of food and agriculture 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Zinc absorption in intestinal system could be strongly affected by the gastrointestinal digestion and absorption of zinc-chelating peptides serving as zinc carriers. In this study, a novel zinc-chelating sea cucumber synthetic peptide (SCSP) was synthesized to estimate its gastrointestinal digestion and promotive effect of zinc absorption in vitro. RESULTS: Analysis of isothermal titration calorimetry suggested that the binding of SCSP and zinc (N ≈ 1) was exothermic, with relatively weak binding affinity (K = 1.0х10-3 mol L-1 ). The formation of SCSP-Zn complexes brought morphological changes to the peptides confirmed by scanning electron microscopy (SEM), which also indicated 6.88% of the existence of zinc element. In addition, the SCSP-Zn complexes remained stable under simulated human gastrointestinal digestion. In vitro study, the SCSP-Zn complex could successfully transport through the intestinal membrane in the model of everted rat gut sacs (nearly 7.5 μM cm-2 ) as well as Caco-2 cells where the zinc transport reached 0.0014 mg mL-1 carried by SCSP. Fluorescence staining experiments revealed free zinc accumulation inside the tissues and cells treated with the SCSP-Zn. CONCLUSIONS: The chelation SCSP-Zn had the promotion ability of zinc absorption in vitro and ex vivo experiments, which suggested a theoretical basis for the design and production of effective zinc chelating peptides as zinc carriers to improve zinc bioavailability. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jsfa.11811

Gastrointestinal digestion and absorption characterization in vitro of zinc-chelating hydrolysate from scallop adductor (Patinopecten yessoensis). 査読国際誌

Jiatong Sun, Xiaoyang Liu, Zixu Wang, Fawen Yin, Huilin Liu, Yoshimasa Nakamura, Chenxu Yu, Dayong Zhou

Journal of the science of food and agriculture 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUD: Zinc is an essential catalytic element in human health system but its absorption in intestinal system could be strongly affected by the gastrointestinal digestion. In this study, the food-derived potential zinc carrier, scallop adductor hydrolysates (SAHs), was produced and characterized. RESULTS: During the temporary storage in 4°C, the SAH decreased in zinc-chelating capacity in aqueous phase whereas the SAH-Zn complex exhibited high stability. Moreover, the secondary structure of SAH had no significant alteration. Zinc morphologically altered the surface structures of SAH, which was involving in carboxyl group of SAH. Results of in vitro gastrointestinal (GI) digestion suggested that the SAH-Zn maintained good stability in GI system and only proportion of high molecular weight cleaved. In addition, SAH could successfully carry and transport zinc while the fluorescence staining revealed free zinc accumulation inside the tissue. Finally, 3 representative absorbed peptides (around 600 Da) were identified and synthesized. Three synthetic peptides exhibit higher zinc-chelating capacity than SAH and could also successfully transported through the intestine. CONCLUSION: This study provided a theoretical basis for the investigation of digestion and absorption of marine animal-derived peptides as zinc carriers. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jsfa.11673

Neither glutamate nor alanine but arginine sensitizes BY-2 cells to arsenate. 査読国際誌

Nur-E-Nazmun Nahar, Md Yeasin Prodhan, Yoshiharu Mimata, Anna Yonezawa, Toshiyuki Nakamura, Yoshimasa Nakamura, Shintaro Munemasa, Yoshiyuki Murata

Bioscience, biotechnology, and biochemistry 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Arsenic is toxic for plants. Our previous results showed that the application of proline enhanced the sensitivity of tobacco BY-2 cells to arsenate. In order to clarify the enhancement mechanism, we investigated the effects of other amino acids on the arsenate-stressed BY-2 cells. Glutamate at up to 10 mM did not affect the cell growth in the absence or presence of arsenate. Arginine at up to 10 mM did not affect the growth in the absence of arsenate but arginine at 10 mM enhanced the inhibition of the cell growth by arsenate. Alanine at up to 10 mM did not affect the cell growth under non-stressed condition but alanine at 10 mM significantly improved the cell growth under arsenate stress. These results suggest that alanine mitigates arsenate stress in BY-2 cells and that arginine like proline enhances the sensitivity of BY-2 cells to arsenate.

DOI： 10.1093/bbb/zbab191

White rice ethanol extract is qualitatively, but not quantitatively, equivalent to that of brown rice as an antioxidant source. 査読国際誌

Hongyan Wu, Toshiyuki Nakamura, Yingnan Guo, Miho Hirooka, Gongliang Zhang, Shintaro Munemasa, Yoshiyuki Murata, Akiko Fujita, Yoshimasa Nakamura

Bioscience, biotechnology, and biochemistry 85 ( 10 ) 2161 - 2168 2021年9月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The purpose of this study is to compare the potentials to exhibit biologically active antioxidant actions between white rice (WR) and brown rice (BR) in in vitro assays and a cellular model. The Trolox equivalent (TE) per 1 mg ethanol extract of WR for the 1,1-diphenyl-2-picrylhydrazyl assay was slightly higher than that of BR, whereas the TE per 1 g whole WR was much lower than that for BR. This tendency was very comparable to those for the oxygen radical absorbance capacity and total polyphenol content. Both of the ethanol extracts also similarly suppressed the hydrogen peroxide-induced cytotoxicity and enhanced the gene expression of drug-metabolizing enzymes. Based on the α-tocopherol quantity, its contribution to the cytoprotective effect of the rice extracts is very limited. Taken together, the ethanol extract of WR might be a qualitatively, but not quantitatively, equivalent source of antioxidative phytochemicals to that of BR.

DOI： 10.1093/bbb/zbab133

Cadmium uptake via apoplastic bypass flow in Oryza sativa. 査読

Izumi C Mori, Carlos Raul Arias-Barreiro, Lia Ooi, Nam-Hee Lee, Muhammad Abdus Sobahan, Yoshimasa Nakamura, Yoshihiko Hirai, Yoshiyuki Murata

Journal of plant research 134 ( 5 ) 1139 - 1148 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

It is known that rice roots take up cadmium (Cd) via the symplastic route mediated by membrane-bound mineral transporters. Here we provide evidence that apoplastic bypass flow is another Cd uptake route in rice. High concentrations of Cd rendered apoplastic bypass flow rate increased in rice seedlings. These concentrations of Cd compromised membrane integrity in the root meristem and transition zone. Polyethleneglycol and proline inhibited the Cd-induced apoplastic bypass flow and Cd transfer to the shoots. Loss-of-function mutant of the Cd uptake transporter, nramp5, showed Cd transport to the shoot comparable to the wild type. At a low Cd concentration, increased apoplastic bypass flow rate by NaCl stress resulted in an elevation of Cd transport to shoots both in the wildtype and nramp5. These observations indicate that apoplastic bypass flow in roots carries Cd transport leading to xylem loading of Cd in addition to the symplastic pathway mediated by mineral transporters under stressed conditions.

DOI： 10.1007/s10265-021-01319-y

Modulation of frequency and height of cytosolic calcium spikes by plasma membrane anion channels in guard cells. 査読国際誌

Md Tahjib-Ul-Arif, Shintaro Munemasa, Toshiyuki Nakamura, Yoshimasa Nakamura, Yoshiyuki Murata

Bioscience, biotechnology, and biochemistry 85 ( 9 ) 2003 - 2010 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cytosolic calcium ([Ca2+]cyt) elevation activates plasma membrane anion channels in guard cells, which is required for stomatal closure. However, involvement of the anion channels in the [Ca2+]cyt elevation remains unclear. We investigated the involvement using Arabidopsis thaliana anion channel mutants, slac1-4 slah3-3 and slac1-4 almt12-1. Extracellular calcium induced stomatal closure in the wild-type plants but not in the anion channel mutant plants whereas extracellular calcium induced [Ca2+]cyt elevation both in the wild-type guard cells and in the mutant guard cells. The peak height and the number of the [Ca2+]cyt spike were lower and larger in the slac1-4 slah3-3 than in the wild type and the height and the number in the slac1-4 almt12-1 were much lower and much larger than in the wild type. These results suggest that the anion channels are involved in the regulation of [Ca2+]cyt elevation in guard cells.

DOI： 10.1093/bbb/zbab118

A multidrug resistance-associated protein inhibitor is a potential enhancer of the benzyl isothiocyanate-induced apoptosis induction in human colorectal cancer cells. 査読国際誌

Qifu Yang, Toshiyuki Nakamura, Masayuki Seto, Miku Miyagawa, Wensi Xu, Beiwei Zhu, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura

Journal of biochemical and molecular toxicology 35 ( 7 ) e22791 2021年7月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The increasing drug efflux through the ATP-binding cassette (ABC) transporters is the most plausible mechanism that mediates resistance to the anticancer phytochemicals, such as benzyl isothiocyanate (BITC), as well as chemotherapy drugs. To identify a potential component to overcome this resistance by combinatory utilization, we focused on multidrug resistance-associated proteins (MRPs) pumping various drug metabolites with glutathione as well as the organic anions. The pharmacological treatment of an MRP inhibitor, MK571, significantly potentiated the BITC-induced antiproliferation, coincided with the enhanced accumulation of BITC and glutathione in human colorectal cancer HCT-116 cells. MK571 also enhanced the apoptosis induction as well as activation of the mitogen-activated protein kinases and caspase-3, whereas it did not affect their basal levels. These results suggested that, since MRPs might play a pivotal role in the BITC efflux, MK571 potentiates the BITC-induced antiproliferation in human colorectal cancer cells through inhibition of the glutathione-dependent BITC efflux.

DOI： 10.1002/jbt.22791

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