Membranes and Cancer Chemotherapy

Cp, Burns

doi:10.3109/07357908809080073

Cited by 25 publications

(1 citation statement)

References 109 publications

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“…The physical state of a cell membrane by virtue of its lipid composition has been implicated in the development and maintenance of MDR (40)(41)(42)(43)(44). The membrane lipid composition is also known to affect the transport of ADR and MITO (45,46).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Parekh¹,

Chitnis²

1990

Selective Cancer Therapeutics

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Utilizing the P388 murine leukemia cells sensitive (P388/S) and resistant (P388/ADR) to Adriamycin (ADR), we evaluated the effect of quinidine, an anti-arrhythmic agent, on the cytotoxic activity of ADR and Mitoxantrone (MITO), both in vitro as well as in vivo. Quinidine enhanced the cytotoxicity of both ADR and MITO in P388/S and P388/ADR cells, as assessed by the decrease in color intensity of formazan crystal in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. A dose dependent inhibition of 3H-thymidine and 3H-uridine incorporation was observed when the P388/S and P388/ADR cells were exposed to quinidine alone. A non-toxic concentration of quinidine (5 microM) enhanced the DNA biosynthesis inhibition induced by ADR (55 to 65%) and MITO (37 to 44%) in P388/ADR cells, indicating reversal of resistance, while in P388/S cells only a minimal increase in DNA biosynthesis inhibition was observed. The combination of quinidine at doses of 50 to 100 mg/kg significantly potentiated the antitumor activity of ADR and MITO in P388/ADR bearing mice, whereas the potentiation of ADR and MITO antitumor response was lower in P388/S bearing mice. Quinidine increased the cellular levels of ADR by 53 to 126% in P388/ADR cells in vitro, but failed to indicate such elevated levels of cellular ADR in P388/S cells. This enhanced intracellular accumulation of ADR in P388/ADR cells, explains the therapeutic efficacy of ADR and MITO in P388/ADR, both in vitro as well as in vivo. Results suggest the efficacy of quinidine to ameliorate the antitumor effects of ADR and MITO in drug resistant tumor cells.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Parekh¹,

Chitnis²

1990

Selective Cancer Therapeutics

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Changes in Plasma Membrane Fluidity of Immortal Rodent Cells Induced by Anticancer Drugs Doxorubicin, Aclarubicin and Mitoxantrone

Jedrzejczak

Koceva‐Chyła

Gwoździński

et al. 1999

Cell Biology International

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The aim of this study was to examine the effect of three structurally different anticancer drugs-the pro-oxidative anthracyclines doxorubicin (DOX) and aclarubicin (ACL), and antioxidative anthraquinone mitoxantrone (MTX) on the fluidity of plasma membrane of immortalized rodent fibroblasts using fluorescence spectroscopy and electron spin resonance (ESR) techniques. Two kinds of fluorescent probes (TMA-DPH and 12-AS) and spin labels (5-DS and methyl-12-DS) were used to monitor fluidity in the hydrophobic core and in the polar headgroup region of the lipid bilayer. Immortalized hamster B14 and NIH 3T3 mouse fibroblasts were exposed to DOX, ACL and MTX. We demonstrate that these drugs influence predominantly the hydrophobic core of the lipid bilayer, inducing significant decrease in its fluidity at low concentrations (2-5 microM). A decreased membrane fluidity at the surface of the lipid bilayer was observed only at a higher concentration (20 microM) of the drugs, which indicates that DOX, ACL and MTX intercalate mainly into the hydrophobic core of the membrane, thereby perturbing its structure.

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Role of Nitric Oxide and Membrane Phospholipid Polyunsaturation in Oxidative Cell Death

Burns

Kelley

Wagner

et al.

Subcellular Biochemistry

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Membranes and Cancer Chemotherapy

Cited by 25 publications

References 109 publications

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Evaluation of Quinidine Effect on the Antitumor Activity of Adriamycin and Mitoxantrone in Adriamycin-Sensitive and -Resistant P388 Leukemia Cells

Changes in Plasma Membrane Fluidity of Immortal Rodent Cells Induced by Anticancer Drugs Doxorubicin, Aclarubicin and Mitoxantrone

Role of Nitric Oxide and Membrane Phospholipid Polyunsaturation in Oxidative Cell Death

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