Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals

Nabekura, Tomohiro; Yamaki, Takeshi; Ueno, K.; Kitagawa, Shuji

doi:10.1007/s00280-007-0676-4

Cited by 112 publications

(71 citation statements)

References 18 publications

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“…17 It also enhances the efficacy of cancer chemotherapy by inhibiting P-glycoprotein and multidrug resistance protein 1 synthesis. 18 However, the precise antitumorigenic mechanisms of glabridin in cancer migration and invasion still remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

et al. 2011

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This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non-small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin's inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of anb3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

et al. 2011

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“…Phytosterols interact with certain ABC proteins, as they are transported in the gut via a complex of ABCG5-ABCG8 or ABCA1 proteins (Raju, 2013). There is some evidence that plant sterols could be a promising group of compounds with potential multidrug resistance ability (El-Readi et al, 2010;Nabekura et al, 2008). This study is a continuation of studies focused on identifying stigmasteryl ester degradation products presented previously by Raczyk et al (2017).…”

Section: Resultsmentioning

confidence: 77%

Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells

Raczyk

Paszel-Jaworska

Rudzińska

2018

Acta Sci Pol Technol Aliment

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Background. Phytosterols are mainly known as a cholesterol-lowering factor, although they form oxidation products during food storage and processing. Moreover, phytosterol oxidation products (POP) can be absorbed and found in human serum, so there is the need to investigate their impact on different kinds of cells. Material and methods. Esters of fatty acids (oleic, linoleic and linolenic) with stigmasterol were synthetized and heated at 180°C, for 1-12 hours. The cytotoxic effect on the leukemic cells of unheated stigmasteryl esters and the mixture of compounds after heating was determined using MTT assays. POP were identified using GC-MS. The total number of POP was analysed by SPE fractionation and GC-FID separation. Dimers, trimers and oligomers in non-polar fraction were determined by gel permeation chromatography with refractive index detection. Results. After heating, stigmasterol oxidation products were formed (up to 1.1 mg/g ester). The heating increased the potency of the compounds to reduce cell population and form POPs and oligomers in a timedependent manner. Conclusion. The cytotoxicity depends on the kind of ester, dose and time. The strongest cytotoxic effect was found after 72 hours of cell treatment. Among the three stigmasteryl esters tested the most cytotoxic effect was caused by stigmasteryl linoleate.

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“…In 1987, it was first detected in human KB carcinoma cells where its overexpression was found to be associated with cellular resistance to a wide range of anticancer drugs including colchincine, vinblastine, and doxorubicin (Ueda et al, 1987). Since then, researchers have compiled a myriad of research reports on the key role of p-gp in MDR (Bhardwaj et al, 2002;Eid et al, 2013;Molnar et al, 2010;Nabekura et al, 2008a;Nabekura et al, 2008b;Perestelo et al, 2011;Yang et al, 2014). It has become an established fact now that p-gp mediates MDR by actively transporting a wide range of anticancer drugs including paclitaxel, doxorubicin, daunorubicin, vinca alkaloids and eteposide (Zhang et al, 2003;Yoshida et al, 2005;Ferreira et al, 2006;Nabekura, 2010a;Yang et al, 2014).…”

Section: Enhancing Activity Of Anticancer Drugs In Multidrug Resistanmentioning

confidence: 99%

Enhancing Activity of Anticancer Drugs in Multidrug Resistant Tumors by Modulating P-Glycoprotein through Dietary Nutraceuticals

Khan¹,

Maryam²,

Mehmood³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

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Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals

Abstract: These results suggest that dietary phytochemicals, such as glycyrrhetinic acid found in licorice, have dual inhibitory effects on P-glycoprotein and MRP1 and might become useful to enhance the efficacy of cancer chemotherapy.

Cited by 112 publications

References 18 publications

Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells

Enhancing Activity of Anticancer Drugs in Multidrug Resistant Tumors by Modulating P-Glycoprotein through Dietary Nutraceuticals

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