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Research ArticleExperimental Studies

Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells

CLAUDIO PLAZA, MARIO PAVANI, RAMIRO ARAYA-MATURANA, JAQUELINE PEZOA, JUAN DIEGO MAYA, ANTONIO MORELLO, MARIA INÉS BECKER, ALFREDO DE IOANNES and JORGE FERREIRA
In Vivo November 2009, 23 (6) 959-967;
CLAUDIO PLAZA
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MARIO PAVANI
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RAMIRO ARAYA-MATURANA
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JAQUELINE PEZOA
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JUAN DIEGO MAYA
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ANTONIO MORELLO
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MARIA INÉS BECKER
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ALFREDO DE IOANNES
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JORGE FERREIRA
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  • For correspondence: jferreir{at}med.uchile.cl
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    Figure 1.

    Effect of DOX combinations with either NDGA or NDGATA on the growth inhibition of TA3 and TA3-MTX-R tumor cells. The line that joins the IC50 of the two drugs used independently indicates the form the plot would take if the effects of the two drugs were additive. IC50 corresponds to the concentration required to inhibit 50% of the culture growth when cells were exposed to DOX for 24 h and NDGA or NDGATA for 3 h. Each value is the mean±SD of four or more independent experiments with each assay performed in triplicate.

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    Figure 2.

    Effect of NDGA and NDGATA on the accumulation of DOX in TA3-MTX-R and TA3 cells. Panel A: Cells exposed to 10 μM DOX in the absence or presence of 100 μM NDGA or 25 μM NDGATA. Data with the same number of asterisks are significantly different at p<0.05 (Student's t-test). Panel B: Effect of NDGA and Panel C: Effect of NDGATA concentration on the DOX accumulation in cells exposed to 10 μM DOX. In Panels B and C: TA3 vs. TA3-MTX-R p<0.05 (one-way ANOVA). DOX was measured in the acid-soluble supernatant after 3 h incubation. Each value is the mean±SD of three independent experiments with each assay performed in triplicate.

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    Figure 3.

    Effect of NDGA and NDGATA on the accumulation and efflux of RHO. Sensitive TA3 and resistant TA3-MTX-R cells were incubated with 1 μM RHO in the presence or absence of NDGA or NDGATA at 37°C for 60 min (accumulation phase), then washed and resuspended in RHO-free medium containing NDGA or NDGATA (efflux phase). Cellular RHO concentration was measured during the accumulation and efflux phases of the experiment. Each point is the mean±SD of at least four independent experiments. Curves marked with the same letters were significantly different from each other and from the control group, p<0.05, by one-way ANOVA.

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    Figure 4.

    Representative ABCB1 expression of TA3 and TA3-MTX-R cell lines. FACS analysis (10,000 cells per assay) was carried out after incubation with anti-Pgp170 goat serum and FITC-labeled anti-goat serum and control untreated. Results correspond to the mean percentage±SE of the total cells expressing ABCB1 (M2 section) from five independent experiments. Student's t-test: p<0.05 TA3 vs. TA3-MTX-R cells.

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    Figure 5.

    Effects of DOX, NDGATA and the combination of NDGATA and DOX on the growth of sensitive TA3 and resistant TA3-MTX-R cell tumors and on the survival of implanted mice. From the fourth day after the tumor cell implantation groups of 10 mice were treated with DOX, NDGATA or DOX and NDGATA or untreated (control). Curves were assessed statistically using one-way ANOVA. Those marked “a” were significantly different from DOX treatment and from the control group, p<0.05.

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November-December 2009
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Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells
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Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells
CLAUDIO PLAZA, MARIO PAVANI, RAMIRO ARAYA-MATURANA, JAQUELINE PEZOA, JUAN DIEGO MAYA, ANTONIO MORELLO, MARIA INÉS BECKER, ALFREDO DE IOANNES, JORGE FERREIRA
In Vivo Nov 2009, 23 (6) 959-967;

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Chemosensitizing Effect of Nordihydroguaiaretic Acid and its Tetra-acetylated Derivative on Parental and Multiresistant TA3 Mouse Mammary Adenocarcinoma Cells
CLAUDIO PLAZA, MARIO PAVANI, RAMIRO ARAYA-MATURANA, JAQUELINE PEZOA, JUAN DIEGO MAYA, ANTONIO MORELLO, MARIA INÉS BECKER, ALFREDO DE IOANNES, JORGE FERREIRA
In Vivo Nov 2009, 23 (6) 959-967;
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