In vitro effect of quercetin on human gastric carcinoma: Targeting cancer cells death and MDR

Borska, Sylwia; Chmielewska, Magdalena; Wysocka, Teresa; Drąg-Zalesińska, Małgorzata; Zabel, Maciej; Dzięgiel, Piotr

doi:10.1016/j.fct.2012.06.035

Cited by 101 publications

(59 citation statements)

References 51 publications

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“…Therefore, studies on substances that enable cancer cell sensitisation to cytostatics are necessary. Such compounds include polyphenols such as resveratrol, curcumin or quercetin (19,36). The effects of polyphenol compounds were studied in human leukaemia cell lines sensitive (K562) and resistant (K562/A02) to DB.…”

Section: Discussionmentioning

confidence: 99%

“…MDR is defined as the insensitivity to therapeutic substances that are not associated by structure or mechanism of action (15,16). 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).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Recent research has shown that more consumption of vegetables and fruits can prevent 20% incident of cancer and about 200,000 cancer related deaths annually (Pratheeshkumar et al, 2012). Other studies have shown that phytochemicals derived from fruits, vegetables, and spices have a great potential to enhance sensitivity of cancer cells to anticancer drugs (Borska et al, 2012;Ye et al, 2012;Kim et al, 2014). A food or a part of food that provide medical and health benefits including the prevention and/or treatment of a disease is called as Nutraceutical (Aggarwal et al, 2009).…”

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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“…The cancer-preventive effects of quercetin have been attributed primarily to its antioxidant activity; it is able to act as a scavenger of radicals and form complexes with metal ions and DNA (9). In addition, a number of studies have demonstrated that quercetin may be a plausible agent for overcoming multidrug resistance, a significant impediment to successful chemotherapy (11).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

et al. 2015

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Abstract. Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer, and oxidative damage is associated with the development of OSCCs. Antioxidants have therefore been proposed for use as chemoprotective agents against different types of cancer. In the present study, the effect of the antioxidant quercetin, administered at doses of 10 and 100 mg/kg/day, was investigated in an experimental murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis. The survival of the treated animals, the plasmatic levels of reduced glutathione and the type and severity of lesions (according the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front) were assessed. Additionally, the organization of the extracellular matrix was analyzed by carbohydrate and collagen histochemistry, and immunohistochemistry was used to assess the expression of the tumor markers proliferating cell nuclear antigen and mutated p53. The results indicate that, despite the promising effect of quercetin in other studies, this drug is ineffective as a chemoprotective agent against 4-NQO-induced OSCC in mice at the assayed doses.

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In vitro effect of quercetin on human gastric carcinoma: Targeting cancer cells death and MDR

Cited by 101 publications

References 51 publications

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

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

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

Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

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