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Down-regulation of P-glycoprotein expression in MDR breast cancer cell MCF-7/ADR by honokiol
1Cancer Institute, The Second Affiliated Hospital, The Medical School, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang Province 310009, People's Republic of China.
Abstract:
P-glycoprotein accounts for the most intrinsic and acquired cancer multidrug resistance. To inhibit the expression of P-glycoprotein is one of the effective ways to reverse cancer drug resistance. Honokiol, a naturally occurring compound, has been demonstrated to combat cancer through mechanisms including inhibition of angiogenesis and induction of apoptosis. Here, we show that honokiol down-regulated the expression of P-glycoprotein at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line. The down-regulation of P-glycoprotein was accompanied with a partial recovery of the intracellular drug accumulation, and of the sensitivities toward adriamycin. This study reveals a novel function of honokiol as an anti-cancer agent.
Insights
Honokiol, a natural compound, reduces P-glycoprotein expression in multidrug-resistant breast cancer cells. This finding offers a new strategy to overcome cancer drug resistance and enhance treatment effectiveness.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- P-glycoprotein mediates multidrug resistance (MDR) in various cancers.
- Inhibiting P-glycoprotein is a key strategy to reverse cancer drug resistance.
- Honokiol exhibits anti-cancer properties, including anti-angiogenesis and apoptosis induction.
Purpose of the Study:
- To investigate the effect of honokiol on P-glycoprotein expression in multidrug-resistant breast cancer cells.
- To determine if honokiol can reverse adriamycin resistance in MCF-7/ADR cells.
Main Methods:
- MCF-7/ADR human breast cancer cells were treated with honokiol.
- P-glycoprotein expression was analyzed at both mRNA and protein levels.
- Intracellular adriamycin accumulation and cell sensitivity were measured.
Main Results:
- Honokiol significantly down-regulated P-glycoprotein expression at mRNA and protein levels.
- This down-regulation led to a partial restoration of intracellular adriamycin accumulation.
- Sensitivity to adriamycin was partially recovered in honokiol-treated cells.
Conclusions:
- Honokiol effectively reduces P-glycoprotein expression in multidrug-resistant breast cancer.
- Honokiol demonstrates potential as an agent to overcome cancer multidrug resistance.
- This study uncovers a novel anti-cancer function of honokiol in reversing drug resistance.
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