Modulation of MDR1 gene expression in multidrug resistant MCF7 cells by low concentrations of small interfering RNAs

Stierlé, Vérène; Laigle, Alain; Jollès, Béatrice

doi:10.1016/j.bcp.2005.08.007

Cited by 28 publications

(23 citation statements)

References 30 publications

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“…SC of sequence 5Ј-MMPMMPPMMMMPMMM-3Ј was coupled with the same procedure as PM to DNM at its 3Ј end. si1 was an siRNA targeting the human MDR1 mRNA at the level of region 88 to 108 relative to the start codon (antisense, 5Ј-UACACUGACAGUUGGUUUCdTdT-3Ј; sense, 5Ј-GAAACCAACUGUCAGUGUAdTdT-3Ј) (Stierlé et al, 2004(Stierlé et al, , 2005). An all-phosphorothioate antisense (AS) oligonucleotide, 5Ј-d(CCATCCCGACCTCGCGCTCC-3Ј), was directed toward the region of the start codon (Ϫ16/ϩ3) (Alahari et al, 1996;Brigui et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

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TargetingMDR1Gene: Synthesis and Cellular Study of Modified Daunomycin-Triplex-Forming Oligonucleotide Conjugates Able to Inhibit Gene Expression in Resistant Cell Lines

Stierlé¹,

Duca²,

Halby³

et al. 2008

Mol Pharmacol

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Reversal of the multidrug-resistant (MDR) phenotype is very important for chemotherapy success. In fact, the expression of the MDR1 gene-encoded P-glycoprotein (P-gp) actively expels antitumor agents such as daunomycin (DNM) out of the cells, resulting in drug resistance. We show that upon conjugation to triplex-forming oligonucleotides, it is possible to address DNM in resistant cells (MCF7-R and NIH-MDR-G185). The oligonucleotide moiety of the conjugate changes the cellular penetra-

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Section: Methodsmentioning

confidence: 99%

“…8). An efficient siRNA (si1) (Stierlé et al, 2004(Stierlé et al, , 2005 and an AS (Brigui et al, 2003) directed against MDR1 were chosen as positive controls. SC-DNM (a scrambled control of PM-DNM) and PM-NH2 [PM containing the linker arm (CH 2 ) 6 -NH 2 in 3Ј and no DNM] were used as negative controls.…”

mentioning

confidence: 99%

TargetingMDR1Gene: Synthesis and Cellular Study of Modified Daunomycin-Triplex-Forming Oligonucleotide Conjugates Able to Inhibit Gene Expression in Resistant Cell Lines

Stierlé¹,

Duca²,

Halby³

et al. 2008

Mol Pharmacol

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“…It is possible that the exclusion of BBR by the MDR1 transporter pgp-170 in HepG2 cells is responsible for its low intracellular accumulation. To test this hypothesis, the uptake of BBR and goldenseal for 2 h in HepG2 cells was measured in the absence and presence of a known MDR1 inhibitor, verapamil (VRPM) (36)(37)(38), at a dose of 0.6 mM. The green fluorescence intensity in BBR-treated cells was increased significantly by VRPM, as demonstrated by direct examination with fluorescence microscopy (Fig.…”

Section: Goldenseal Increases Ldlr Expression Through the Concerted Amentioning

confidence: 98%

The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms

Abidi

Chen

Kraemer

et al. 2006

Journal of Lipid Research

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Our previous studies have identified berberine (BBR), an alkaloid isolated from the Chinese herb huanglian, as a unique cholesterol-lowering drug that upregulates hepatic low density lipoprotein receptor (LDLR) expression through a mechanism of mRNA stabilization. Here, we demonstrate that the root extract of goldenseal, a BBR-containing medicinal plant, is highly effective in upregulation of liver LDLR expression in HepG2 cells and in reducing plasma cholesterol and low density lipoprotein cholesterol (LDL-c) in hyperlipidemic hamsters, with greater activities than the pure compound BBR. By conducting bioassay-driven semipurifications, we demonstrate that the higher potency of goldenseal is achieved through concerted actions of multiple bioactive compounds in addition to BBR. We identify canadine (CND) and two other constituents of goldenseal as new upregulators of LDLR expression. We further show that the activity of BBR on LDLR expression is attenuated by multiple drug resistance-1 (MDR1)-mediated efflux from liver cells, whereas CND is resistant to MDR1. This finding defines a molecular mechanism for the higher activity of CND than BBR. We also provide substantial evidence to show that goldenseal contains natural MDR1 antagonist(s) that accentuate the upregulatory effect of BBR on LDLR mRNA expression. These new findings identify goldenseal as a natural LDL-c-lowering agent, and our studies provide a molecular basis for the mechanisms of action.-Abidi, P., W. Chen, F. B. Kraemer, H. Li, and J. Liu. The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.

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“…6,29 The use of such a low siRNA concentration also is important for minimizing nonspecific (ie, off-target) siRNA activity. [32][33][34] With multiple siRNA treatments over 24-hour intervals, $40% to 50% P-gp suppression was gained after 72 hours using PLL-StA and Lipofectamine 2000.…”

Section: Original Article 5550mentioning

confidence: 99%

“…Nonviral delivery approaches could be more feasible in a clinical setting given their suitability for scale-up and their minimal, if any, immunogenicity. Nonviral siRNA delivery using lipid-based carriers has resulted in significant P-gp suppression in some reports 6,7,20 ; however, a clear functional outcome, namely, increased intracellular accumulation and cytotoxic effect of drugs, has not been clearly demonstrated. Moreover, these carriers are intended for siRNA delivery in culture and display relatively weak protection of siRNA against serum 21 ; thus, they are not suitable for systemic administration.…”

mentioning

confidence: 99%

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

Abbasi¹,

Lavasanifar²,

Berthiaume³

et al. 2010

Cancer

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BACKGROUND: Among the treatment options that have been developed for cancer, chemotherapy remains 1 of the leading clinical approaches. Chemotherapy can usually control tumor growth at the onset of disease, but its effectiveness becomes limited by the overexpression of transporter proteins responsible for drug efflux, leading to multidrug resistance (MDR). To overcome this obstacle, the authors explored the feasibility of down-regulating the main drug transporter, Pglycoprotein (P-gp), by using nonviral small interfering RNA (siRNA) delivery as means to enhance the accumulation of chemotherapeutic agents in drug-resistant cancer cells. METHODS: Several cationic carriers capable of siRNA complexation were investigated for P-gp down-regulation in the MDA435/LCC6 cell line and, consequently, increased cellular uptake of the chemotherapeutic agents doxorubicin and paclitaxel. RESULTS: Efficient siRNA delivery into tumor cells was demonstrated particularly using a palmitic-acid substituted poly(L-lysine), with no apparent differences in siRNA delivery between the wild type (WT)-expressing and P-gp-expressing phenotype (MDR1) of the cells. Efficient siRNA delivery led to approximately 40% to 50% P-gp suppression (based on the average expression level of the protein), an approximately 3-fold increased DOX uptake, and increased cytotoxicity in MDR1 cells. CONCLUSIONS: The authors concluded that effective siRNA delivery with nonviral carriers can reduce the level of P-gp on cell surfaces and enhance the efficiency of chemotherapeutic agents in vitro. Cancer 2010;116:5544-54.

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Modulation of MDR1 gene expression in multidrug resistant MCF7 cells by low concentrations of small interfering RNAs

Cited by 28 publications

References 30 publications

TargetingMDR1Gene: Synthesis and Cellular Study of Modified Daunomycin-Triplex-Forming Oligonucleotide Conjugates Able to Inhibit Gene Expression in Resistant Cell Lines

TargetingMDR1Gene: Synthesis and Cellular Study of Modified Daunomycin-Triplex-Forming Oligonucleotide Conjugates Able to Inhibit Gene Expression in Resistant Cell Lines

The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

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