Accumulation of degradation products of doxorubicin and pirarubicin formed in cell culture medium within sensitive and resistant cells

Fiallo, Marina; Laigle, Alain; Borrel, Marie-Nicole; Garnier‐Suillerot, Arlette

doi:10.1016/0006-2952(93)90140-r

Cited by 26 publications

(35 citation statements)

References 13 publications

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“…We have found that the conjugates showed many advantages in comparison with the unmodified antibiotics and other agents: lower toxicity, stronger antitumor (antileukemic) effect and higher therapeutic index. Our experimental results are in good agreement with the data of other investigators (5,6,7,8,9). By our working hypothesis, the conjugates of antitumor drugs might also overcome the multiple drug resistance of tumor cells (MDR) in vitro and in vivo (10,11,12).…”

Section: Resultssupporting

confidence: 94%

Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

Todorova

Maneva

Ilarionova

et al. 2003

Biotechnology & Biotechnological Equipment

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Section: Resultssupporting

confidence: 94%

Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

Todorova

Maneva

Ilarionova

et al. 2003

Biotechnology & Biotechnological Equipment

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“…During this incubation time, doxorubicin may efflux from the cell, be diluted by growth, or be degraded. Doxorubicin fluorescence is known to be quenched once bound to DNA, resulting in a 30–40‐fold decrease in fluorescence signal . It has also been shown that some doxorubicin degradation products fluoresce in the same emission wavelength window as doxorubicin .…”

Section: Discussionmentioning

confidence: 99%

“…Doxorubicin fluorescence is known to be quenched once bound to DNA, resulting in a 30–40‐fold decrease in fluorescence signal . It has also been shown that some doxorubicin degradation products fluoresce in the same emission wavelength window as doxorubicin . Single‐cell IC 50 values provide a snapshot of the order of magnitude of intracellular doxorubicin molecules, but the interpretation of the exact quantitative values should consider these factors.…”

Section: Discussionmentioning

confidence: 99%

A Flow Cytometric Clonogenic Assay Reveals the Single-Cell Potency of Doxorubicin

Maass

Kulkarni

Quadir

et al. 2015

Journal of Pharmaceutical Sciences

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Standard cell proliferation assays use bulk media drug concentration to ascertain the potency of chemotherapeutic drugs; however, the relevant quantity is clearly the amount of drug actually taken up by the cell. To address this discrepancy, we have developed a flow cytometric clonogenic assay to correlate the amount of drug in a single cell with the cell’s ability to proliferate using a cell tracing dye and doxorubicin, a naturally fluorescent chemotherapeutic drug. By varying doxorubicin concentration in the media, length of treatment time, and treatment with verapamil, an efflux pump inhibitor, we introduced 105 – 1010 doxorubicin molecules per cell; then used a dye-dilution assay to simultaneously assess the number of cell divisions. We find that a cell’s ability to proliferate is a surprisingly conserved function of the number of intracellular doxorubicin molecules, resulting in single-cell IC50 values of 4 – 12 million intracellular doxorubicin molecules. The developed assay is a straightforward method for understanding a drug’s single-cell potency and can be used for any fluorescent or fluorescently-labeled drug, including nanoparticles or antibody-drug conjugates.

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“…7D for comparison). In contrast, inversion of the 560-nm/592-nm intensity ratio has been observed in relation to doxorubicin degradation (Fiallo et al, 1993). Therefore, the enhancement of the peak at ϳ560 nm in the cytoplasm when using OFA (Fig.…”

mentioning

confidence: 93%

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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Accumulation of degradation products of doxorubicin and pirarubicin formed in cell culture medium within sensitive and resistant cells

Cited by 26 publications

References 13 publications

Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

A Flow Cytometric Clonogenic Assay Reveals the Single-Cell Potency of Doxorubicin

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

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