Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites

Scambia, Giovanni; Ranelletti, F O; Panici, P. Benedetti; Piantelli, Mauro; Bonanno, Giuseppina; Vincenzo, Rosa De; Ferrandina, Gabriella; Pierelli, Luca; Capelli, A.; Mancuso, Stefano

doi:10.1007/bf00685531

Cited by 115 publications

(49 citation statements)

References 27 publications

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“…All cultures were incubated at 37°C under 5% carbon dioxide: 95% air in a high-humidity atmosphere. The MCF-7 ADRr and CEM-VBLr cell lines exhibit the classical MDR phenotype [mdr-1 mRNA and P-glycoprotein (P-gp) overexpression] and are ER negative (Berman et al, 1991;Scambia et al, 1991 …”

Section: Materials and Methods Drugsmentioning

confidence: 99%

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis

Ferlini

Scambia²,

Distefano³

et al. 1997

Br J Cancer

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Summary The taxanes are a promising family of anti-tumour drugs that block cell cycle replication by interfering with the microtubule network. The clinical use of these drugs involves some problems related to their low solubility and occurrence of resistance, which is mainly dependent on the multidrug-resistant (MDR) phenotype. To investigate the possible interaction between docetaxel and tamoxifen (TAM), three oestrogen receptor-negative cancer cell lines, MDR-MDA-MB 231, MDR + CEM-VBLr and MCF-7 ADRr, were used. In all three cell lines, the combination of docetaxel and TAM was more effective in terms of growth inhibition than single drug exposure. Isobolic analysis confirmed the presence of synergism in all cell lines when docetaxel was used at 0.2 gM and TAM at a dose equal to or higher than 1 gM. Flow cytometric DNA analysis performed on the three cell lines showed that TAM was able to increase the G/M blocking activity of docetaxel. This blocking activity was followed by an increased flow cytometric DNA fragmentation suggestive of the presence of apoptosis, which was confirmed by DNA gel fragmentation and morphological analysis. While an antagonistic effect on P-glycoprotein (P-gp) activity may contribute to the synergistic effect of tamoxifen and docetaxel on CEM-VBLr and MCF-7 ADRr, other mechanisms must be involved, as the synergistic effect is also apparent with a P-gp-negative cell line.Keywords: docetaxel; tamoxifen; apoptosis; cell cycleThe taxanes are a new class of cytotoxic agents the cellular target of which is the microtubule network. Their mechanism of action is considered to be the enhancement of tubuline polymerization in both the initiation and elongation of microtubules (Schiff et al, 1979). In this way, taxanes induce extensive formation of microtubule bundles, thereby blocking cell replication at a checkpoint between G2 and M phase of the cell cycle. Paclitaxel (formerly called taxol) and docetaxel (formerly called taxotere) were the first members of the taxane family to be developed and have been approved by the US Food and Drug Administration for the treatment of ovarian and breast cancer respectively. Phase II trials are now in progress to extend their application to a wide variety of carcinomas, including lung, colon, head and neck, prostate, cervical and brain cancer (Mastropaolo et al, 1995). However, despite this encouraging therapeutic potential, the clinical use of these drugs involved some problems related to the solubility, toxicity and development of drug resistance, the last-named mainly dependent on an increased MDR activity (Bhalla et al, 1994). In an attempt to minimize these problems, two complementary strategies can be employed: paclitaxel and docetaxel analogues with a better therapeutic efficacy and less toxicity can be developed and possible synergism with other chemotherapeutics can be investigated.The aim of this study was to test the in vitro efficacy of docetaxel in association with the anti-oestrogen tamoxifen (TAM). (Leonessa et al, 1994) and vinblastine (Trump...

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Section: Materials and Methods Drugsmentioning

confidence: 99%

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis

Ferlini

Scambia²,

Distefano³

et al. 1997

Br J Cancer

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“…Quercetin acts as an anti-proliferative agent by inhibiting cell proliferation, cell growth, and cessation of cell cycle of colon, breast, gastric, oral, prostate and ovarian cancer cells [104][105][106][107][108][109][110]. Studies on kaempferol are few but are contradictory as their proliferative/ anti-proliferative activity is based on its concentration.…”

Section: Dietary Fibersmentioning

confidence: 99%

An Insight of Pulses: From Food to Cancer Treatment

Vohra¹,

Dureja²,

Garg³

2016

J Pharmacogn Nat Prod

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“…All cultures were incubated at 37 °C under 5% carbon dioxide, 95% air in a high humidity atmosphere. The MCF-7 ADRr and CEM VBLr cell lines exhibit the classical MDR phenotype (mdr-1 mRNA and P-gp over-expression) and were ER-negative (Berman et al 1991, Scambia et al 1991. For the experiments described herein, drugs (ADR and VBL) were removed 2 weeks prior to an experiment.…”

Section: Cell Culturesmentioning

confidence: 99%

The synergistic anti-tumour activity of ICI 182,780 in combination with docetaxel is mediated by P-glycoprotein inhibition

Ferlini¹

1998

Endocrine Related Cancer

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Docetaxel is a semi-synthetic drug that has been shown to be effective in refractory advanced breast cancer. Its main mechanism of action seems to be to block microtubule depolymerisation. In this study we investigated the interaction between docetaxel and the pure anti-oestrogen ICI 182,780 on different oestrogen receptor-negative cancer cells, some of which express the classical multi-drug resistance (MDR) phenotype. ICI 182,780 potentiated the anti-proliferative effect of docetaxel only in the MDRpositive cells. Isobolic analysis demonstrated that this chemosensitising effect was a synergism. In the same conditions where synergism was detected, cell cycle analysis demonstrated an augmentation of cells blocked at the G2/M phase of the cell cycle, suggesting that ICI 182,780 increases the activity of docetaxel. In order to test this hypothesis, we performed bcl-2 western blot analysis and demonstrated that the addition of ICI 182,780 to docetaxel induced bcl-2 phosphorylation only in MDR-positive cells. The functional inactivation of bcl-2 is probably responsible for the commitment to apoptosis, since the combined docetaxel/ICI 182,780 treatment was able to foster a massive apoptosis in MDR-bearing cells as demonstrated by morphological analysis.Our results suggest that the synergism between docetaxel and ICI 182,870 is due to a block in Pglycoprotein activity, thus determining cell cycle block, bcl-2 inactivation and apoptosis induced by Endocrine-Related Cancer (1998) 5 315-324 docetaxel accumulation. C Ferlini et al.: Synergism between docetaxel and ICI 182,780 on human cancer cells 316 oestrogens as down-modulators of the P-gp function is an attractive approach to improve the efficacy of docetaxelbased anti-tumour therapy.The aim of this study was to investigate the in vitro efficacy of docetaxel in combination with the pure antioestrogen ICI 182,780 on different oestrogen receptor (ER)-negative cancer cell lines, some of which express the multi-drug resistant (MDR) phenotype. Results indicate that, in MDR-bearing cells, the combination treatment of docetaxel/ICI 182,780 presents a significant synergism in terms of growth inhibition, cell cycle block, bcl-2 phosphorylation and induction of apoptosis. Materials and methodsDrugs Docetaxel (kindly provided by Dr Bombardelli, Indena, Italy) was solubilised in dimethyl sulphoxide (DMSO; stock solution 10 mM) and used within 7 days. The control cells were treated with the same amount of vehicle alone. ICI 182,780 and tamoxifen (TAM) stock solutions (100 mM) (kindly provided by Dr Isola, Zeneca, Italy) were made up in absolute DMSO, and were used at concentrations ranging from 0.1 to 100 µM. The final DMSO concentration never exceeded 0.2% (v/v) in either control or treated samples. Cell culturesTwo breast cancer cell lines (MDA-MB 231 and MCF-7 ADRr) and two leukaemia cell lines (CEM and CEM VBLr) were used. The MDA-MB 231 cell line was purchased from the American Type Culture Collection (Rockville, MD, USA); the MDR-positive MCF-7 ADRr cell line, sel...

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Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites

Cited by 115 publications

References 27 publications

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis

An Insight of Pulses: From Food to Cancer Treatment

The synergistic anti-tumour activity of ICI 182,780 in combination with docetaxel is mediated by P-glycoprotein inhibition

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