The effect of quercetin and doxorubicin combination in inhibiting resistance in mcf-7 cell

Desrini, Sufi; Mustofa, .; Sholikhah, Eti Nurwening

doi:10.3329/bjms.v16i1.31139

Cited by 8 publications

(11 citation statements)

References 20 publications

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“…Silymarin as a complex is generally known for its inhibitory effects on P-gp transporter [46][47][48]. Also, the combination of one silymarin component-quercetin with doxorubicin-significantly increased the doxorubicin sensitivity of doxorubicin-resistant breast cancer (MCF-7) cells and quercetin also decreased P-gp expression [49]. We noticed strong P-gp ATPase inhibition activity of all silybins and dehydrosilybins in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 65%

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

et al. 2020

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Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

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Section: Discussionmentioning

confidence: 65%

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

et al. 2020

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“…The most commonly used breast cancer resistant 2D cell culture model is the MCF-7/ ADR cells. [36,65,66] These cells are generally obtained by maintaining MCF-7 cells in culture medium supplemented with DOX for long periods of time. [33,34,36] For instance, Desrini et al obtained Doxorubicin resistant MCF-7 cell by exposing parental MCF-7 cells to DOX twice a week for a period of 25 days.…”

Section: Resultsmentioning

confidence: 99%

“…[36,65,66] These cells are generally obtained by maintaining MCF-7 cells in culture medium supplemented with DOX for long periods of time. [33,34,36] For instance, Desrini et al obtained Doxorubicin resistant MCF-7 cell by exposing parental MCF-7 cells to DOX twice a week for a period of 25 days. [36] Optionally, resistant MCF-7 cells can also be obtained by exposing them to hypoxic cycles (e.g., <1% oxygen), [37,38] since the hypoxia triggers the activation of a plethora of molecular pathways involved in cancer cells' resistance (reviewed in refs.…”

Section: Resultsmentioning

confidence: 99%

“…[24,25,27] On the other hand, researchers are developing drug resistant 2D cell cultures. [7,[33][34][35][36][37][38][39][40] These models show a drug resistance profile more alike to that found in in vivo tumors and can be analyzed through standardized assays and equipment used for conventional 2D cell cultures. Recently, Koshkin et al demonstrated that 3Dderived MCF-7 cells (cells obtained from 3D spheroids disaggregation) are able to preserve their 3D-phenotype when cultured in 2D.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of 2D Cell Cultures Derived From 3D MCF‐7 Spheroids Displaying a Doxorubicin Resistant Profile

Nunes

Costa

Barros

et al. 2018

Biotechnology Journal

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In vitro 3D cancer spheroids generally exhibit a drug resistance profile similar to that found in solid tumors. Due to this property, these models are an appealing for anticancer compounds screening. Nevertheless, the techniques and methods aimed for drug discovery are mostly standardized for cells cultured in 2D. The development of 2D cell culture models displaying a drug resistant profile is required to mimic the in vivo tumors, while the equipment, techniques, and methodologies established for conventional 2D cell cultures can continue to be employed in compound screening. In this work, the response of 3D-derived MCF-7 cells subsequently cultured in 2D in medium supplemented with glutathione (GSH) (antioxidant agent found in high levels in breast cancer tissues and a promoter of cancer cells resistance) to Doxorubicin (DOX) is evaluated. These cells demonstrated a resistance toward DOX closer to that displayed by 3D spheroids, which is higher than that exhibited by standard 2D cell cultures. In fact, the 50% inhibitory concentration (IC 50 ) of DOX in 3D-derived MCF-7 cell cultures supplemented with GSH is about eight-times higher than that obtained for conventional 2D cell cultures (cultured without GSH), and is only about two-times lower than that attained for 3D MCF-7 spheroids (cultured without GSH). Further investigation revealed that this improved resistance of 3D-derived MCF-7 cells may result from their increased P-glycoprotein (P-gp) activity and reduced production of intracellular reactive oxygen species (ROS).

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“…It has been known for a long time that flavonoids can modulate both expression and activity of many ABC transporters, with some relevant impact on drug resistance [ 20 , 21 , 22 ]. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family such as P-gp [ 23 , 24 , 25 , 26 , 27 , 28 ], ABCC1 [ 27 , 29 ], ABCC2, and ABCG2 [ 27 ]. ABCC6 is a member of the C subfamily of ATP-binding cassette transporters mainly expressed in liver and kidney, poorly involved in drug resistance [ 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration

Abruzzese¹,

Matera²,

Martinelli³

et al. 2021

IJMS

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Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5′-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids.

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The effect of quercetin and doxorubicin combination in inhibiting resistance in mcf-7 cell

Cited by 8 publications

References 20 publications

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

Establishment of 2D Cell Cultures Derived From 3D MCF‐7 Spheroids Displaying a Doxorubicin Resistant Profile

Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration

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