The network of P-glycoprotein and microRNAs interactions

Lopes-Rodrigues, Vanessa; Seca, Hugo; Sousa, Diana; Sousa, Emília; Lima, Raquel T.; Vasconcelos, M. Helena

doi:10.1002/ijc.28500

Cited by 59 publications

(46 citation statements)

References 179 publications

(225 reference statements)

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“…Interestingly, all the polyoxygenated steroids investigated for antitumor [66], antibacterial [64], antifungal [64], and reversing MDR [62] activities contain the characteristic 3β,5α,6β-hydroxyl moiety. Among these derivatives are a spiroketal hippurinstanol (14), hippuristerone (15), which possesses a 3-keto group, and the cyclopropane-containing gorgosterols (16)(17)(18)(19)(20) (Figure 4) [62,64]. Polyoxygenated steroids 14-20 also differ in the side chains.…”

Section: Polyoxygenated Steroids and Derivativesmentioning

confidence: 99%

“…Among these derivatives are a spiroketal hippurinstanol (14), hippuristerone (15), which possesses a 3-keto group, and the cyclopropane-containing gorgosterols (16)(17)(18)(19)(20) (Figure 4) [62,64]. Polyoxygenated steroids 14-20 also differ in the side chains.…”

Section: Polyoxygenated Steroids and Derivativesmentioning

confidence: 99%

“…P-gp is encoded by the human MDR-1 gene, which is located at chromosome 7. It contains 1280 amino acids, arranged in two halves, each encompassing a transmembrane domain (TMD) which spans the membrane and an intracellular nucleotide-binding domain (NBD) [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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Section: Polyoxygenated Steroids and Derivativesmentioning

confidence: 99%

Section: Polyoxygenated Steroids and Derivativesmentioning

confidence: 99%

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Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…1,2 The main genes investigated are those that encode drug-metabolism enzymes 3 ; study of the expression of P-glycoprotein (P-gp), which contributes to the multidrug resistance phenotype, is a clear example (for a review, see Lopes-Rodrigues et al 4 ). P-gp is a transmembrane drug transporter encoded by the multidrug resistance 1 (MDR1) gene; it acts as an efflux pump that works in an adenosine triphosphate (ATP)-dependent fashion.…”

Section: Introductionmentioning

confidence: 99%

Association study between the MDR1 gene and clinical characteristics in schizophrenia

Tovilla-Zárate¹,

Vargas

Hernández

et al. 2014

Rev. Bras. Psiquiatr.

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Objective: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. Methods: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. Results: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. Conclusion: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings.

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“…The classical mechanism of MDR is associated with the overexpression of the ATP binding cassette subfamily B member 1 (ABCB1) gene enco ding P-glycoprotein (P-gp), which contributes to the reduction of the effective drug concentration in the cell by transporting the drug out of the cell (14,15,(17)(18)(19)(20). In addition to the classical MDR mechanism associated with overexpression of P-gp, there are atypical mechanisms (21)(22)(23). Examples of these atypical mechanisms include the overexpression of Annexin A1 (ANXA1) and thioredoxin (TXN) proteins.…”

Section: Introductionmentioning

confidence: 99%

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

et al. 2018

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Abstract. Multidrug resistance (MDR) is a notable problem in the use of chemotherapy. Therefore, studies aimed at identifying substances capable of overcoming resistance of cancer cells are required. Examples of these compounds are polyphenols, including resveratrol, that exert a range of various biological activities. The aim of the present study was to demonstrate the effect of 3,5,4'-trihydroxy-trans-stilbene (resveratrol) on the expression of ATP binding cassette subfamily B member 1, Annexin A1 (ANXA1) and thioredoxin (TXN) genes, and the proteins encoded by these genes, which are associated with MDR. The experiments were performed in human gastric cancer cell lines EPG85-257RDB (RDB) and EPG85-257RNOV (RNOV), which are resistant to daunorubicin and mitoxantrone, respectively, in addition to EPG85-257P (control), which is sensitive to cytostatic drugs. Cells were treated with 30 or 50 µM resveratrol for 72 h and changes in the expression levels of the genes were analysed with the use of a reverse transcription-quantitative polymerase chain reaction. The cellular levels of P-glycoprotein (P-gp), ANXA1 and TXN were evaluated using immunofluorescence and western blot analysis. Resveratrol in both concentrations has been shown to have a statistically significant influence on expression of the mentioned genes, compared with untreated cells. In RDB cells, resveratrol reduced the expression level of all analyzed genes, compared with untreated cells. Similar results at the protein level were obtained for P-gp and TXN. In turn, in the RNOV cell line, resveratrol reduced TXN expression at mRNA and protein levels, compared with untreated cells. The results of the present study indicate that resveratrol may reduce the resistance of cancer cells by affecting the expression of a number of the genes and proteins associated with MDR. IntroductionResveratrol belongs to the stilbenoid group of polyphenols, possessing two phenol rings linked to each other by an ethylene bridge (1). In 1940, resveratrol was isolated from the root of Veratrum grandiflorum (1,2). A primary dietary source of resveratrol is red wine, as a very high resveratrol concentration is present in the skin of red grapes (50-100 µg/g) (3). In natural conditions, resveratrol is synthesized by plants in response to external environmental factors, including ultraviolet radiation and heavy metals (3,4). Resveratrol is identified in two isomeric forms, cis and trans-resveratrol ( Fig. 1) (5,6).The trans form is dominant in terms of its prevalence and biological activity (7). The hydrophobic nature of resveratrol considerably contributes to its limited bioavailability (8).Owing to the varied biological activity of resveratrol, it has been the subject of numerous studies aimed at revealing its health-enhancing properties, and its use in prevention and treatment of many diseases (1,3,5,9). The results of in vitro and in vivo studies have proved that resveratrol exhibits anticancer activity at all three stages of the oncogenic process: initiation, promotion and progr...

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The network of P-glycoprotein and microRNAs interactions

Cited by 59 publications

References 179 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

Association study between the MDR1 gene and clinical characteristics in schizophrenia

Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol

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