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P-glycoprotein breast cancer mdr

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https://www.readbyqxmd.com/read/29303075/abc-transporters-regulation-and-association-with-multidrug-resistance-in-hepatocellular-carcinoma-and-colorectal-carcinoma
#1
Maria Paula Ceballos Mancini, Juan Pablo Rigalli, Lucila Ines Cere, Mariana Semeniuk, Viviana Alicia Catania, Maria Laura Ruiz
For most cancers, the treatment of choice is still being chemotherapy despite of its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to an overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) that limit the efficacy of chemotherapeutic drugs...
January 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29181822/schisandrin-a-reverses-doxorubicin-resistant-human-breast-cancer-cell-line-by-the-inhibition-of-p65-and-stat3-phosphorylation
#2
Zong-Lin Zhang, Qing-Cheng Jiang, Su-Rong Wang
BACKGROUND: Multidrug resistance (MDR) in breast cancer therapy occurs frequently. Thus, anti-MDR agents from natural products or synthetic compounds were tested extensively. We have also explored the reverse effect and mechanism of Schisandrin A (Sch A), a natural product, on MCF-7 breast cancer doxorubicin (DOX)-resistant subline MCF-7/DOX. METHODS: MTT assay was performed to measure the viability of MCF-7 cells to assess the reverse effect of Sch A. Western blot analysis was used to study the protein levels...
November 27, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29181060/expression-of-multidrug-resistance-protein-p-glycoprotein-in-correlation-with-markers-of-hypoxia-hif-1%C3%AE-epo-epo-r-in-invasive-breast-cancer-with-metastasis-to-lymph-nodes
#3
Anna M Badowska-Kozakiewicz, Maria Sobol, Janusz Patera
Introduction: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) - a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29077148/the-effect-of-saikosaponin-d-on-doxorubicin-pharmacokinetics-and-its-mdr-reversal-in-mcf-7-adr-cell-xenografts
#4
C Li, H-G Xue, L-J Feng, M-L Wang, P Wang, X-D Gai
OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29050217/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
#5
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...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016119/9-deazapurines-as-broad-spectrum-inhibitors-of-the-abc-transport-proteins-p-glycoprotein-multidrug-resistance-associated-protein-1-and-breast-cancer-resistance-protein
#6
Katja Stefan, Sven Marcel Schmitt, Michael Wiese
P-Glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2) are the three major ABC transport proteins conferring resistance to many structurally diverse anticancer agents, leading to the phenomenon called multidrug resistance (MDR). Much effort has been put into the development of clinically useful compounds to reverse MDR. Broad-spectrum inhibitors of ABC transport proteins can be of great use in cancers that simultaneously coexpress two or three transporters...
October 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28987325/anti-tumor-compound-ry10-4-suppresses-multidrug-resistance-in-mcf-7-adr-cells-by-inhibiting-pi3k-akt-nf-%C3%AE%C2%BAb-signaling
#7
Xiaofan Yang, Yufeng Ding, Miao Xiao, Xin Liu, Jinlan Ruan, Pingping Xue
RY10-4, an anti-tumor agent, exerts cytotoxicity to various human cancer cell lines. However, few studies reported the effect of combined application of RY10-4 and chemotherapeutic drugs against cancer cells with multidrug resistance (MDR). In this study, P-glycoprotein (P-gp), which is reported to mediate MDR to anti-cancer drugs, was proved to be overexpressed in the adriamycin (ADR)-resistant human breast cancer cells, namely MCF-7/ADR cells. Furthermore, RY10-4 application resulted in a downregulation of P-gp in MCF-7/ADR cells, thus leading to higher chemosensitivity to ADR...
October 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28919756/polymeric-mixed-micelles-loaded-mitoxantrone-for-overcoming-multidrug-resistance-in-breast-cancer-via-photodynamic-therapy
#8
Zeyong Li, Yuee Cai, Yiqiao Zhao, Hua Yu, Haiyu Zhou, Meiwan Chen
Mitoxantrone (MIT) is an anticancer agent with photosensitive properties that is commonly used in various cancers. Multidrug resistance (MDR) effect has been an obstacle to using MIT for cancer therapy. Photochemical internalization, on account of photodynamic therapy, has been applied to improve the therapeutic effect of cancers with MDR effect. In this study, an MIT-poly(ε-caprolactone)-pluronic F68-poly(ε-caprolactone)/poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) (MIT-PFP/PPP) mixed micelles system was applied to reverse the effect of MDR in MCF-7/ADR cells via photochemical reaction when exposed to near-infrared light...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28782465/pyramidatine-z88-sensitizes-vincristine-resistant-human-oral-cancer-kb-vcr-cells-to-chemotherapeutic-agents-by-inhibition-of-p-glycoprotein
#9
Zulong Liu, Hengrui Zhu, Shijin Qu, Lisha Tang, Lihuan Cao, Wenbo Yu, Xianmei Yang, Songmin Jiang, Dayuan Zhu, Changheng Tan, Long Yu
Multi-drug resistance (MDR) to anticancer drugs remains a major impediment in cancer therapy. A major goal for scientists is to identify more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. Here, we reported that Pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, had potent anti-MDR activity. The average resistant fold (RF) of Z88 is 0.09 and 0.51 in KB/VCR (vincristine-resistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells...
August 3, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28748603/graphene-quantum-dots-downregulate-multiple-multidrug-resistant-genes-via-interacting-with-their-c-rich-promoters
#10
Chao Luo, Yanfang Li, Lijuan Guo, Fangwei Zhang, Hui Liu, Jiali Zhang, Jing Zheng, Jingyan Zhang, Shouwu Guo
Multidrug resistance (MDR) is the major factor in the failure of many forms of chemotherapy, mostly due to the increased efflux of anticancer drugs that mediated by ATP-binding cassette (ABC) transporters. Therefore, inhibiting ABC transporters is one of effective methods of overcoming MDR. However, high enrichment of ABC transporters in cells and their broad substrate spectra made to circumvent MDR are almost insurmountable by a single specific ABC transporter inhibitor. Here, this study demonstrates that graphene quantum dots (GQDs) could downregulate the expressions of P-glycoprotein, multidrug resistance protein MRP1, and breast cancer resistance protein genes via interacting with C-rich regions of their promoters...
July 27, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28700899/pegylated-liposomal-formulation-of-doxorubicin-overcomes-drug-resistance-in-a-genetically-engineered-mouse-model-of-breast-cancer
#11
András Füredi, Kornélia Szebényi, Szilárd Tóth, Mihály Cserepes, Lilla Hámori, Veronika Nagy, Edina Karai, Péter Vajdovich, Tímea Imre, Pál Szabó, Dávid Szüts, József Tóvári, Gergely Szakács
Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil®/Caelyx®) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#12
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28632894/flavonoids-as-modulators-of-metabolic-enzymes-and-drug-transporters
#13
REVIEW
Anca Miron, Ana Clara Aprotosoaie, Adriana Trifan, Jianbo Xiao
Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs))...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28570027/structure-activity-relationship-studies-on-6-7-dimethoxy-2-phenethyl-1-2-3-4-tetrahydroisoquinoline-derivatives-as-multidrug-resistance-reversers
#14
Elisabetta Teodori, Silvia Dei, Gianluca Bartolucci, Maria Grazia Perrone, Dina Manetti, Maria Novella Romanelli, Marialessandra Contino, Nicola Antonio Colabufo
A series of derivatives were synthesized and studied with the aim to investigate the structure-activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar. Then, different aryl-substituted amides were inserted, and to explore the effects of varying the amide function, the corresponding isosteric ester derivatives and some alkylamine analogues were synthesized. The new compounds were studied to evaluate their P-gp interaction profile and selectivity toward the two other ABC transporters, multidrug-resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP)...
August 22, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28554760/reversal-of-p-glycoprotein-mediated-multidrug-resistance-is-induced-by-saikosaponin-d-in-breast-cancer-mcf-7-adriamycin-cells
#15
Chun Li, Xingang Guan, Haogang Xue, Peng Wang, Manli Wang, Xiaodong Gai
Multidrug resistance (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene is major obstacles for successful cancer chemotherapy. P-gp could extrude anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. MDR reversal agents for P-gp can restore the sensitivity of MDR cells to such drugs. Saikosaponin D (SSd), one of the major triterpenoid saponins derived from Bupleurum chinense DC (BCDC), has been shown to possess anti-inflammatory, anti-infectious and anti-tumor properties...
February 3, 2017: Pathology, Research and Practice
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
#16
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
#17
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...
August 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
#18
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...
June 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
#19
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
#20
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
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