Quercetin: A potential drug to reverse multidrug resistance

Chen, Chen; Zhou, Jane; Ji, Chunyan

doi:10.1016/j.lfs.2010.07.004

Cited by 199 publications

(128 citation statements)

References 89 publications

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“…Recently, there has been a proposal of a new generation of ABC inhibitors which focuses on natural products and natural product mimics [28][29][30], peptidomimetics [31], surfactants and lipids [32], and dual ligands [20]. While the traditional sources of terrestrial plants and microbes will undoubtedly continue to yield valuable new bioactive agents, it is even more important to explore all available pools of molecular diversity.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…However, QC has low oral bioavailability [2] . For instance, its absorption in the gastrointestinal tract (GIT) is low due to low solubility in water [8] . Also, QC is metabolized immediately through enzymatic hydrolysis [9] in GIT when administered orally.…”

Section: Research Papermentioning

confidence: 99%

“…Also, QC is metabolized immediately through enzymatic hydrolysis [9] in GIT when administered orally. It is also glucuronidated, sulphated and methylated [8][9][10] . More than 95 % of QC absorbed is metabolized by hepatic metabolism [6,10] and is eliminated from the intestinal cells through an efflux pump mechanism [10] .…”

Section: Research Papermentioning

confidence: 99%

In vitro Penetration and Bioavailability of Novel Transdermal Quercetin-loaded Ethosomal Gel

Ramadon¹,

Anwar²,

Harahap³

2017

pharmaceutical-sciences

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Quercetin has been widely used to treat many diseases because of its high antioxidant activity. However, it has low oral bioavailability and penetration through the skin. The aim of this research was to enhance penetration and bioavailability of quercetin using transdermal ethosomal gel. Three ethosomal formulae, E1 (1 %), E2 (1.5 %) and E3 (2 %) with different concentration of quercetin were prepared using thin-film hydration method. Their physical properties were characterized, and then a selected ethosomal formula was incorporated into a gel dosage form. Two gels, one ethosomal and the other non-ethosomal were prepared. In vitro penetration using Franz diffusion cells and bioavailability study in Sprague Dawley male rats were carried out. Results showed that E2 was the chosen formula to be incorporated into the gel dosage form. According to the in vitro penetration study, the diffusion flux of quercetin from the ethosomal and non-ethosomal gels were 343.35±17.69 ng/cm 2 /h and 120.68±11.92 ng/cm 2 /h, respectively (P<0.05). In the bioavailability study, ethosomal gel showed higher maximum concentration (C max ) and area under curve (AUC 0-t ) when compared to non-ethosomal gel and oral suspension. C max from the ethosomal gel, nonethosomal gel, and oral suspension were 413.49±28.64, 189.46±49.68, and 61.92±14.31 ng/ml, respectively (P<0.05). AUC 0-t from the ethosomal gel, non-ethosomal gel, and oral suspension were 4035.15±560.60, 584.87±265.46, and 431.21±239.85, respectively (P<0.05). In conclusion, ethosomal gel could increase penetration and bioavailability of quercetin compared to non-ethosomal gel.

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“…MG-63 cells were cultured in 6-well plates at a concentration of 2x10 5 cells/ well and treated with various concentrations of quercetin for 48 h. The activities of caspase-9 and caspase-3 were determined by a colorimetric assay using the caspase-9 and caspase-3 activation kits (Invitrogen) according to the manufacturer's instructions. Briefly, the cells were lysed with provided lysis buffer for 30 min on ice and centrifuged at 16000 x g for 10 min.…”

Section: Measurement Of Apoptosis By Flow Cytometry Analysis Withmentioning

confidence: 99%

“…Hence the challenge of seeking new therapeutic approaches that can further improve the efficiency and alleviate the adverse effects is clear and urgent (4). Epidemiological studies have shown that regular consumption of tea, vegetables and fruits is associated with reduced risk of cancer (5). Quercetin with a molecular formula of C 15 H 10 O 7 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells

2011

Mol Med Report

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Abstract. Quercetin (a natural polyphenolic compound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer cell lines, including the human osteosarcoma cell line, MG-63. However, its effects on osteosarcoma cell apoptosis are still undefined. The present study was undertaken to examine the effect of quercetin on cell viability, apoptosis and mitochondrial membrane potential, and to determine the molecular mechanism of quercetininduced apoptosis by investigating the expression of Bcl-2 family proteins (Bcl-2, Bax), cytochrome C, caspase-9 and caspase-3 in MG-63 cells. We found that quercetin suppressed the viability of MG-63 cells in a dose-and time-dependent manner. Furthermore, we observed that quercetin induced the loss of mitochondrial membrane potential, upregulated the expression of the proapoptotic proteins, Bax and cytochrome C, and activated caspase-9 and caspase-3, and downregulated the expression of antiapoptotic protein, Bcl-2. These data suggest that quercetin may induce apoptosis via the mitochondrial-dependent pathway in MG-63 cells. IntroductionOsteosarcoma (OS) is the third most common cancer in childhood and adolescents, and the most common primary malignant bone tumor (1). With the development of new chemotherapy protocols, surgical techniques and radiological staging, the 5-year survival and cure rates have increased to 60-80% in patients with localized disease (2). However, major problems associated with chemotherapy still remain, particularly the frequent development of drug resistance (3). Moreover, chemotherapy may induce DNA mutations in normal cells. Hence the challenge of seeking new therapeutic approaches that can further improve the efficiency and alleviate the adverse effects is clear and urgent (4). Epidemiological studies have shown that regular consumption of tea, vegetables and fruits is associated with reduced risk of cancer (5). Quercetin with a molecular formula of C 15 H 10 O 7 (Fig. 1), is an abundant flavonoid in tea, fruits and vegetables (6). Quercetin has been shown to induce cell death by apoptosis in many human cancer cell lines, such as hepatoma, oral, leukemia, lung and colon cancer cell lines (7,8).Apoptotic cell death is an innate cellular response to eliminate abnormal or redundant cells in mammals and hence is crucial for mammal development and tissue homeostasis (9). The disturbed regulation of this vital process represents a major causative factor in the pathogenesis of cancers, including OS (10,11). The mitochondrial-dependent pathway is one of the apoptotic pathways in mammalian cells. Mitochondrial membrane permeabilization, accompanied by the collapse of electrochemical gradient across the mitochondrial membrane causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from the mitochondria, leading to cell apoptosis (12,13). Bcl-2 family proteins serve as critical regulators of this pathway through their influe...

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Quercetin: A potential drug to reverse multidrug resistance

Cited by 199 publications

References 89 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

In vitro Penetration and Bioavailability of Novel Transdermal Quercetin-loaded Ethosomal Gel

Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells

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