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P-glycoprotein breast cancer mdr

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https://www.readbyqxmd.com/read/28488578/triterpenoids-from-aglaia-abbreviata-exert-cytotoxicity-and-multidrug-resistant-reversal-effect-in-mcf-7-adm-cells-via-reactive-oxygen-species-induction-and-p-glycoprotein-inhibition
#1
Juan Cen, Beibei Zheng, Rubing Bai, Li Zhang, Feng Zhang, Xia Zhang
Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and AA-6 (2) from stems of Aglaia abbreviata, and studied their cytotoxicity in multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA-6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing reactive oxygen species (ROS) with depressed mitochondrial membrane potential and caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the intracellular antioxidant systems, involving Glutathione S-Transferase π, Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed Akt/NF-E2-related factor 2 pathway...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28462502/mechanistically-elucidating-the-in-vitro-safety-and-efficacy-of-a-novel-doxorubicin-derivative
#2
Samaa Alrushaid, Yunqi Zhao, Casey L Sayre, Zaid H Maayah, M Laird Forrest, Sanjeewa N Senadheera, Kevin Chaboyer, Hope D Anderson, Ayman O S El-Kadi, Neal M Davies
Doxorubicin is an effective anticancer drug; however, it is cardiotoxic and has poor oral bioavazilability. Quercetin is a plant-based flavonoid with inhibitory effects on P-glycoprotein (P-gp) and CYP3A4 and also antioxidant properties. To mitigate these therapeutic barriers, DoxQ, a novel derivative of doxorubicin, was synthesized by conjugating quercetin to doxorubicin. The purpose of this study is to mechanistically elucidate the in vitro safety and efficacy of DoxQ. Drug release in vitro and cellular uptake by multidrug-resistant canine kidney (MDCK-MDR) cells were quantified by HPLC...
May 1, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28425219/resistance-modifying-activity-in-vinblastine-resistant-human-breast-cancer-cells-by-oligosaccharides-obtained-from-mucilage-of-chia-seeds-salvia-hispanica
#3
Daniel G Rosas-Ramírez, Mabel Fragoso-Serrano, Sonia Escandón-Rivera, Alba L Vargas-Ramírez, Juan P Reyes-Grajeda, Manuel Soriano-García
The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells...
April 20, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28381801/association-of-single-nucleotide-polymorphisms-in-stat3-abcb1-and-abcg2-with-stomatitis-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-sunitinib-a-retrospective-analysis-in-japanese-patients
#4
Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai
Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28363522/reversal-of-multidrug-resistance-by-marsdenia-tenacissima-and-its-main-active-ingredients-polyoxypregnanes
#5
Kenneth K W To, Xu Wu, Chun Yin, Stella Chai, Sheng Yao, Onat Kadioglu, Thomas Efferth, Yang Ye, Ge Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs...
May 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28212576/galectin-1-knockdown-improves-drug-sensitivity-of-breast-cancer-by-reducing-p-glycoprotein-expression-through-inhibiting-the-raf-1-ap-1-signaling-pathway
#6
Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052008/targeting-p-glycoprotein-function-p53-and-energy-metabolism-combination-of-metformin-and-2-deoxyglucose-reverses-the-multidrug-resistance-of-mcf-7-dox-cells-to-doxorubicin
#7
Chaojun Xue, Changyuan Wang, Yaoting Sun, Qiang Meng, Zhihao Liu, Xiaokui Huo, Pengyuan Sun, Huijun Sun, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Kexin Liu
Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28005280/abcg2-bcrp-specific-and-nonspecific-modulators
#8
REVIEW
Diana Peña-Solórzano, Simone Alexandra Stark, Burkhard König, Cesar Augusto Sierra, Cristian Ochoa-Puentes
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2)...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28000875/fulvestrant-reverses-doxorubicin-resistance-in-multidrug-resistant-breast-cell-lines-independent-of-estrogen-receptor-expression
#9
Yuan Huang, Donghai Jiang, Meihua Sui, Xiaojia Wang, Weimin Fan
Drug resistance, a major obstacle to successful cancer chemotherapy, frequently occurs in recurrent or metastatic breast cancer and results in poor clinical response. Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer. In this study, we evaluated the combination treatment of fulvestrant and doxorubicin in ER-negative multidrug-resistant (MDR) breast cancer cell lines Bads‑200 and Bats‑72. Fulvestrant potentiated doxorubicin-induced cytotoxicity, apoptosis and G2/M arrest with upregulation of cyclin B1...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27956367/systematic-evaluation-of-multifunctional-paclitaxel-loaded-polymeric-mixed-micelles-as-a-potential-anticancer-remedy-to-overcome-multidrug-resistance
#10
Jiulong Zhang, Xiufeng Zhao, Qing Chen, Xiaoyi Yin, Xiu Xin, Kexin Li, Mingxi Qiao, Haiyang Hu, Dawei Chen, Xiuli Zhao
Multidrug resistance (MDR) of tumor cells is becoming the main reason for the failure of chemotherapy and P-glycoprotein (P-gp) mediated drug efflux has demonstrated to be the key factor for MDR. To address this issue, a novel pH-responsive mixed micelles drug delivery system composed of dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) and folate acid-D-α-tocopheryl polyethylene glycol 2000 (FA-TPGS2K) copolymers has been designed for the delivery of antitumor agent, paclitaxel (PTX) via FA-receptor mediated cell endocytosis, into PTX-resistant breast cancer MCF-7 cells (MCF-7/PTX)...
December 9, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27906043/exosomes-play-an-important-role-in-the-process-of-psoralen-reverse-multidrug-resistance-of-breast-cancer
#11
Xiaohong Wang, Chengfeng Xu, Yitong Hua, Leitao Sun, Kai Cheng, Zhongming Jia, Yong Han, Jianli Dong, Yuzhen Cui, Zhenlin Yang
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo)...
December 1, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27810353/pyrrolopyrimidine-derivatives-and-purine-analogs-as-novel-activators-of-multidrug-resistance-associated-protein-1-mrp1-abcc1
#12
Sven Marcel Schmitt, Katja Stefan, Michael Wiese
Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27779650/hoxb4-knockdown-reverses-multidrug-resistance-of-human-myelogenous-leukemia-k562-adm-cells-by-downregulating-p-gp-mrp1-and-bcrp-expression-via-pi3k-akt-signaling-pathway
#13
Hong Wang, Xiu-Hong Jia, Jie-Ru Chen, Ying-Jie Yi, Jian-Yong Wang, You-Jie Li, Shu-Yang Xie
Multidrug resistance (MDR) plays a pivotal role in human chronic myelogenous leukemia (CML) chemotherapy failure. MDR is mainly associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) proteins. Phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) expression in many human malignancies...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27754360/rack1-mediates-the-interaction-of-p-glycoprotein-with-anxa2-and-regulates-migration-and-invasion-of-multidrug-resistant-breast-cancer-cells
#14
Yi Yang, Na Wu, Zhiyong Wang, Fei Zhang, Ran Tian, Wei Ji, Xiubao Ren, Ruifang Niu
The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation...
October 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27744704/one-step-self-assembling-nanomicelles-for-pirarubicin-delivery-to-overcome-multidrug-resistance-in-breast-cancer
#15
Yanping Li, Rui Li, Qinhui Liu, Wenyao Li, Ting Zhang, Min Zou, Hong Li, Tong Wu, Shihai Cheng, Zhiguang Su, Zhirong Zhang, Jinhan He
Tumor cells can acquire multidrug resistance (MDR) as a result of drug efflux mediated by P-glycoprotein (P-gp). Here we report a targeted delivery system to carry pirarubicin (THP) to MDR breast cancer both in vitro and in vivo. PEG-derivatized vitamin E (PAMV6) amphiphiles loaded with THP were self-assembled in a single step. The PAMV6 micelles showed unimodal size distribution and high drug loading efficiency. Cytotoxicity of PAMV6/THP was higher than that of free THP on MCF-7/ADR cells but comparable to that of THP on MCF-7 cells...
November 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27601896/synergistic-and-complete-reversal-of-the-multidrug-resistance-of-mitoxantrone-hydrochloride-by-three-in-one-multifunctional-lipid-sodium-glycocholate-nanocarriers-based-on-simultaneous-bcrp-and-bcl-2-inhibition
#16
Guixia Ling, Tianhong Zhang, Peng Zhang, Jin Sun, Zhonggui He
Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA - BCRP inhibitor), and GcNa (Bcl-2 inhibitor)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27596118/co-encapsulation-of-paclitaxel-and-baicalein-in-nanoemulsions-to-overcome-multidrug-resistance-via-oxidative-stress-augmentation-and-p-glycoprotein-inhibition
#17
COMPARATIVE STUDY
Luhua Meng, Xuejun Xia, Yanfang Yang, Jun Ye, Wujun Dong, Panpan Ma, Yiqun Jin, Yuling Liu
Multidrug resistance (MDR) is a major obstacle for clinical application of paclitaxel (PTX). Recent studies have suggested that baicalein (BA) might be a potent MDR reversal agent with the ability of P-glycoprotein inhibition and oxidative stress augmentation. Herein, we co-encapsulated PTX and BA in nanoemulsions (PTX/BA NE) for overcoming MDR in breast cancer. Paclitaxel-cholesterol complex and baicalein-phospholipid complex were prepared to improve the liposolubility of PTX and BA. The cytotoxicity of the combination of PTX and BA with different weight ratios were evaluated and the combination with a weight ratio of 1/1 exhibited the strongest synergistic effect...
November 20, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27585695/grid-independent-descriptors-grind-analysis-and-sar-guided-molecular-docking-studies-to-probe-selectivity-profiles-of-inhibitors-of-multidrug-resistance-transporters-abcb1-and-abcg2
#18
Talha Shafi, Ishrat Jabeen
BACKGROUND: ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinants of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs...
2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27581212/reversal-of-p-glycoprotein-mediated-multidrug-resistance-by-doxorubicin-and-quinine-co-loaded-liposomes-in-tumor-cells
#19
Qiying Shen, Liyan Qiu
Multidrug resistance (MDR) is a major obstacle to successful clinical cancer chemotherapy. Currently, there is still unsatisfactory demand for innovative strategies as well as effective and safe reversing agent to overcome MDR. In this study, we developed a novel nanoformulation, in which doxorubicin hydrochloride (DOX) and quinine hydrochloride (QN) were simultaneously loaded into liposomes by a pH-gradient method for overcoming MDR and enhancing cytotoxicity in a doxorubicin-resistant human breast cancer cell line (MCF-7/ADR)...
October 11, 2016: Journal of Liposome Research
https://www.readbyqxmd.com/read/27566201/a-myrsinol-diterpene-isolated-from-a-traditional-herbal-medicine-langdu-reverses-multidrug-resistance-in-breast-cancer-cells
#20
Huapeng Wang, Xiaobo Chen, Ting Li, Jing Xu, Yonggang Ma
ETHNOPHARMACOLOGICAL RELEVANCE: LANGDU, a Chinese traditional herbal medicine, was the dried roots of Euphorbia prolifera Buch-Ham. The herbal medicine has been used as anti-cancer and anti-inflammatory drug in local folk medicine for several hundred years. AIM OF THE STUDY: P-glycoprotein (P-gp) is a transmembrane exporter, which can expel a variety of anti-cancer drugs. Over-expressed P-glycoprotein in cancer cells impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR)...
December 24, 2016: Journal of Ethnopharmacology
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