Establishment and Use of Human Mouth Epidermal Carcinoma (KB) Cells Overexpressing P-Glycoprotein To Characterize Structure Requirements for Flavonoids Transported by the Efflux Transporter

Fang, Yajing; Xia, Mengmeng; Liang, Fuqiang; Cao, Weiwei; Pan, Siyi; Xu, Xiaoyun

doi:10.1021/acs.jafc.9b00039

Cited by 12 publications

(20 citation statements)

References 42 publications

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“…The results indicated that P-gp was overexpressed in KB/MDR1 cells and functioned normally. This finding is consistent with our previous research [26]. Thus, the evaluation results of the cell are effective.…”

Section: Discussionsupporting

confidence: 94%

Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

et al. 2019

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P-glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance (MDR) in cancer cells. In order to enhance the uptake of chemotherapy drugs, larger amounts of P-gp inhibitors are required. Besides several chemically synthesized P-gp inhibitors, flavonoids as P-gp inhibitors are being investigated, with their advantages including abundance in our daily diet and a low toxicity. The cytotoxicity of daunorubicin (as a substrate of P-gp) to KB/MDR1 cells and the parental KB cells was measured in the presence or absence of flavonoids. A two-dimensional quantitative structure–activity relationship (2D-QSAR) model was built with a high cross-validation coefficient (Q2) value of 0.829. Descriptors including vsurf_DW23, E_sol, Dipole and vsurf_G were determined to be related to the inhibitory activity of flavonoids. The lack of 2,3-double bond, 3′-OH, 4′-OH and the increased number of methoxylated substitutions were shown to be beneficial for the inhibition of P-gp. These results are important for the screening of flavonoids for inhibitory activity on P-gp.

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Section: Discussionsupporting

confidence: 94%

Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

et al. 2019

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“…Djiogue et al (2009) reported that genistein containing C5-OH had stronger binding ability to the estrogen receptor than daidzein, which further proved that C5-OH was an active site of flavonoids. Fang et al (2019) found that C3-OH, C5-OH, C3′-OCH 3 , and C4′-OCH 3 had good activity for the binding of flavonoids to P-Glycoprotein. Liu et al (2012) studied the inhibitory effect of polymethoxyflavones (PFM) on Aspergillus Niger in citrus.…”

Section: Discussionmentioning

confidence: 94%

“…We speculated that the C5-OH of ring A is the key site for citrinin reduction. Fischer et al (2012) studied the effects of genistein and daidzein on the immunity of Caenorhabditis elegans. It was concluded that genistein decreased vitellogenin expression, but daidzein increased vitellogenin expression, which showed different trends, which may be related to C5-OH.…”

Section: Discussionmentioning

confidence: 99%

Effects of some flavonoids on the mycotoxin citrinin reduction by Monascus aurantiacus Li AS3.4384 during liquid-state fermentation

et al. 2020

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Monascus can produce many beneficial metabolites; however, it can simultaneously also produce citrinin, which seriously limits its application. Therefore, reducing the production of citrinin is of great interest. Herein, Monascus aurantiacus Li AS3.4384 (MAL) was used to optimize the liquid-state fermentation process and investigate the effects of genistein and other flavonoids on citrinin, pigments, and biomass of MAL. Results showed that citrinin decreased by 80%, pigments and biomass increased by approximately 20% in 12 days with addition of 20.0 g/L rice powder as a carbon source and 2.0 g/L genistein during shaking liquid-state fermentation. Further, genistein, daidzein, luteolin, apigenin, quercetin, baicalein, kaempferol myricetin, and genistin exerted different effects on citrinin production by MAL, with genistein causing the highest reduction in citrinin production during liquid-state fermentation, possibly due to the presence of C5-OH, C4′-OH, and C7-OH. Therefore, genistein can be added to the fermentation process of Monascus to reduce citrinin.

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“…Molecular docking was also performed to investigate the structure-affinity relationship between P-gp and the flavonoids. The results indicated that 3-OH, 5-OH, 39-OCH3, and 49-OCH3 are crucial for the interplay between flavonoids and P-gp (Fang et al, 2019). Epigallocatechin-3-gallate could downregulate the expression level of P-gp and BCRP but could not affect the expression of MDR-associated protein 1 in Adriamycin (ADR)-resistant human leukemia (CEM/ADR) cells (Li et al, 2018).…”

Section: Traditional Chinese Medicine Modulation Of P-gpmentioning

confidence: 97%

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

et al. 2020

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As a member of the ATP-dependent membrane transport proteins, P-Glycoprotein (P-gp) is known to pump substrates out of cells using an ATP-dependent mechanism. The overexpression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the efficacy of extensive antitumor drugs and leads to multidrug resistance (MDR) clinically. The combination of anticancer drugs with P-gp inhibitor has been an attractive and promising strategy to reverse MDR in cancer treatment. However, nonspecific or nonselective distribution of P-gp inhibitors to nontarget organs is one of the most fatal shortcomings in clinical application. Thus, there is an urgent need for effective and nontoxic MDR reversal agents, particularly in P-gp-mediated MDR. Traditional Chinese medicine (TCM) natural products may prove less toxic for use in P-gp inhibition to promote MDR reversal. P-gp modulatory effects have been previously demonstrated using selected TCM, including the flavonoid, alkaloid, terpenoid, coumarin, and quinonoid compounds, and some Chinese medicine extracts. Moreover, the approaches for screening active components from TCM are necessary, and these approaches face challenges. At present, the approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo, and in silico methods. This review will provide an overview and update on the role of TCM in overcoming P-gp-mediated MDR and the approaches to study the interaction between TCM and P-gp. SIGNIFICANCE STATEMENT This review summarized some traditional Chinese medicines identified to have a modulatory effect on P-gp, including flavonoids, alkaloids, terpenoids, coumarins, quinonoid compounds, and some Chinese medicine extracts, and it introduced possible mechanisms. The approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo, and in silico methods.

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Establishment and Use of Human Mouth Epidermal Carcinoma (KB) Cells Overexpressing P-Glycoprotein To Characterize Structure Requirements for Flavonoids Transported by the Efflux Transporter

Cited by 12 publications

References 42 publications

Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

Effects of some flavonoids on the mycotoxin citrinin reduction by Monascus aurantiacus Li AS3.4384 during liquid-state fermentation

The Effects of Traditional Chinese Medicine on P-Glycoprotein–Mediated Multidrug Resistance and Approaches for Studying the Herb–P-Glycoprotein Interactions

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