Adriamycin

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Don R. Phillips - One of the best experts on this subject based on the ideXlab platform.

  • detection of Adriamycin dna adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
    Nucleic Acids Research, 2008
    Co-Authors: Kate E. Coldwell, Suzanne M. Cutts, Ted Ognibene, Paul T. Henderson, Don R. Phillips
    Abstract:

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  • Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
    Nucleic acids research, 2008
    Co-Authors: Kate E. Coldwell, Suzanne M. Cutts, Ted Ognibene, Paul T. Henderson, Don R. Phillips
    Abstract:

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

Peiqing Liu - One of the best experts on this subject based on the ideXlab platform.

  • tanshinone iia protects neonatal rat cardiomyocytes from Adriamycin induced apoptosis
    Translational Research, 2008
    Co-Authors: Jie Gao, Guoqing Yang, Ping Wang, Huijie Zhang, Shaorui Chen, Peiqing Liu
    Abstract:

    Tanshinone IIA (TSN) is a monomer extracted from the Chinese herb Danshen. In this study, we examined the effect of Tanshinone IIA on Adriamycin (ADR)-induced apoptosis in neonatal rat cardiomyocytes and underlying molecular mechanisms. Primary cultured cardiomyocytes were treated with 1 micromol/L of Adriamycin for 24 h with or without pretreatment with Tanshinone IIA (0.5-2 micromol/L) for 2 h. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, and flow cytometry measurement were used to assess cell viability and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and dihydroethidium were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the expression of Bcl-2 and Bax proteins. Adriamycin significantly induced apoptosis in cardiomyocytes. Tanshinone IIA (0.5-2 micromol/L) ameliorated apoptosis induced by Adriamycin in a dose-dependent manner. Tanshinone IIA (2 micromol/L) markedly attenuated Adriamycin-induced reactive oxygen species production. Western blotting revealed that Tanshinone IIA prevented the Adriamycin-mediated reduction of the ratio of Bcl-2/Bax. In conclusion, Tanshinone IIA significantly inhibits Adriamycin-induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect is at least partly caused by its antioxidant properties.

Kate E. Coldwell - One of the best experts on this subject based on the ideXlab platform.

  • detection of Adriamycin dna adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
    Nucleic Acids Research, 2008
    Co-Authors: Kate E. Coldwell, Suzanne M. Cutts, Ted Ognibene, Paul T. Henderson, Don R. Phillips
    Abstract:

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  • Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
    Nucleic acids research, 2008
    Co-Authors: Kate E. Coldwell, Suzanne M. Cutts, Ted Ognibene, Paul T. Henderson, Don R. Phillips
    Abstract:

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

Robert M. Sutherland - One of the best experts on this subject based on the ideXlab platform.

  • Resistance to verapamil sensitization of multidrug-resistant cells grown as multicellular spheroids.
    International journal of cancer, 1994
    Co-Authors: Koh‐ichi Sakata, Tim T. Kwok, G. Ross Gordon, Nahid Waleh, Robert M. Sutherland
    Abstract:

    The ability of verapamil to overcome resistance to Adriamycin in a multidrug-resistant derivative of the V79 cell line (LZ), grown as multicellular spheroids or as monolayers, was examined. Verapamil was much less effective in overcoming resistance to Adriamycin in spheroids than in monolayers. Verapamil increased the Adriamycin content of cells grown as monolayers, but had no significant effect on the drug content of spheroids. This occurred in spite of the same mdr-I mRNA and protein levels in monolayers and spheroids. When the surviving fraction of cells was normalized to the cellular Adriamycin content, cells both in monolayers and spheroids treated with verapamil were still more sensitive to Adriamycin than their counterparts not treated with verapamil. The observed resistance of spheroids to Adriamycin and verapamil sensitization may be caused by a drug-resistance mechanism that is functional only in spheroids, in addition to the activity of P-glycoprotein. Multicellular tissue architecture and cell-cell contact may play significant roles in this type of multidrug-resistance mechanism.

Jie Gao - One of the best experts on this subject based on the ideXlab platform.

  • tanshinone iia protects neonatal rat cardiomyocytes from Adriamycin induced apoptosis
    Translational Research, 2008
    Co-Authors: Jie Gao, Guoqing Yang, Ping Wang, Huijie Zhang, Shaorui Chen, Peiqing Liu
    Abstract:

    Tanshinone IIA (TSN) is a monomer extracted from the Chinese herb Danshen. In this study, we examined the effect of Tanshinone IIA on Adriamycin (ADR)-induced apoptosis in neonatal rat cardiomyocytes and underlying molecular mechanisms. Primary cultured cardiomyocytes were treated with 1 micromol/L of Adriamycin for 24 h with or without pretreatment with Tanshinone IIA (0.5-2 micromol/L) for 2 h. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, and flow cytometry measurement were used to assess cell viability and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and dihydroethidium were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the expression of Bcl-2 and Bax proteins. Adriamycin significantly induced apoptosis in cardiomyocytes. Tanshinone IIA (0.5-2 micromol/L) ameliorated apoptosis induced by Adriamycin in a dose-dependent manner. Tanshinone IIA (2 micromol/L) markedly attenuated Adriamycin-induced reactive oxygen species production. Western blotting revealed that Tanshinone IIA prevented the Adriamycin-mediated reduction of the ratio of Bcl-2/Bax. In conclusion, Tanshinone IIA significantly inhibits Adriamycin-induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect is at least partly caused by its antioxidant properties.