Membrane alterations associated with progressive adriamycin resistance

Wheeler, Candace; Rader, Richard L.; Kessel, David

doi:10.1016/0006-2952(82)90723-7

Cited by 62 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, MDR is associated with increased sensitivity (collateral sensitivity) to membrane active agents, such as non-ionic detergents, local anaesthetics and steroids (Bech-Hansen et al, 1976;Riordan & Ling, 1985). Changes in membrane permeability (Riordan & Ling, 1985), composition , ultrastructure (Arsenault et al, 1988), and the physical properties of the membrane bilayer (Wheeler et al, 1982;Ramu et al, 1983;Siegfried et al, 1983, Kessel, 1988 have also been reported. All of these observations suggest that the overexpression of P-glycoprotein leads to perturbations in membrane structure and function, perhaps arising in part from the insertion of a large hydrophobic protein into the plasma membrane.…”

mentioning

confidence: 99%

Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Loe

Sharom²

1993

Br J Cancer

View full text Add to dashboard Cite

Summary The interaction of membrane-active amphiphiles with a series of MDR Chinese hamster ovary (CHO) cell lines was investigated. Cross-resistance to cationic amphiphiles was observed, which was effectively sensitised by verapamil. MDR cells showed collateral sensitivity to polyoxyethylene amphiphiles (Triton X-100/Nonidet P40), which reached a maximum at 9-10 ethylene oxide units. Resistant lines were also highly collaterally sensitive (17-fold) to dibutylphthalate. mdrl transfectants showed cross-resistance to cationic amphiphiles, but no collateral sensitivity to nonionic species. Triton X-100/Nonidet P-40 inhibited 3H-azidopine photoaffinity labelling at low concentrations, perhaps reflecting a specific interaction with Pglycoprotein.Further investigation of the molecular basis of collateral sensitivity revealed that association of 3H-Triton X-100 with MDR cells reached steady state levels rapidly, and occurred by a non-mediated mechanism. The equilibrium level of X-100 uptake was inversely related to drug resistance. Collateral sensitivity is thus not a result of decreased Triton X-100 association with the cell.The fluorescent probe merocyanine 540 was used to examine the MDR plasma membrane microenvironment for physicochemical changes. Increasing levels of drug resistance correlated with a progressive shift in the mean cell fluorescence to lower levels, which suggests that the packing density in the outer leaflet of MDR cells is increased relative to that of the drug-sensitive parent.

show abstract

mentioning

confidence: 99%

Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Loe

Sharom²

1993

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Several studies have suggested that changes in the plasma membrane structure and lipid composition are associated with the development of drug resistance in cell lines in vitro (Peterson et al, 1983;Rintoul & Center, 1984;Wheeler et al, 1982). The degree of structural order of plasma membrane lipids was found to be higher in doxorubicin resistant P388 murine leukaemia cells than in drug sensitive parental cells (Ramu et al, 1983) and a correlation between membrane fluidity and resistance to doxorubicin was observed in a series of Sarcoma 180 sublines (Siegfried et al, 1983).…”

mentioning

confidence: 99%

Effect of polyunsaturated fatty acids on the drug sensitivity of human tumour cell lines resistant to either cisplatin or doxorubicin

Plumb

Luo²,

Kerr³

1993

Br J Cancer

View full text Add to dashboard Cite

Summary Growth of cells in vitro in the presence of fatty acids can alter the membrane composition and hence fluidity and permeability. Exposure of both doxorubicin (2780AD) and cisplatin (2780CP) resistant human ovarian cell lines to non-toxic concentrations of polyunsaturated fatty acids (y-linolenic acid and eicosapentaenoic acid) either before or during exposure to the cytotoxic drug did not modulate drug sensitivity. However, the fatty acids were toxic in their own right. Whilst the ovarian cell lines 2780AD and 2780CP showed a small degree of cross resistance to both fatty acids the doxorubicin resistant breast cell line MCF7/Adr was slightly more sensitive than MCF7. When the interactions between the polyunsaturated fatty acids and cytotoxic drugs were analysed by the isobologram method the toxicities were shown to be additive.

show abstract

“…These include phospholipid structure, glycoprotein synthesis, the transport of small molecules and ions, and membrane fluidity. With respect to membrane fluidity, an attempt has been made to correlate it with the relative amount of oxygen present, and with the development of drug resistance (125). Under hypoxic conditions, there was an increase in fluidity that did not correlate with differences in membrane perneability to the anthracyclines.…”

Section: Membrane Association As a Cytotoxic Eventmentioning

confidence: 99%

A chemical perspective on the anthracycline antitumor antibiotics.

Abdella¹,

Fisher²

1985

Environ Health Perspect

View full text Add to dashboard Cite

The anthracycline antitumor antibiotics occupy a central position in the chemotherapeutic control of cancer. They remain, however, antibiotics of the last resort and thus exhibit toxicity both to the neoplasm and to the host organism. As part of the continuing effort to dissociate the molecular processes responsible for these two separate toxicities, attention has been drawn to the intrinsic redox capacity of their tetrahydronapthacenedione aglycone moiety, and to the possible expression of this redox activity against those biomolecules for which anthracyclines have a particular affinity (polynucleotides and membranes). This review is a synopsis of the present trends and thoughts concerning this relationship, written from the point of view of the intrinsic chemical competence of the anthracyclines and their metabolites. While our ignorance is profound-the precise molecular locus of the antitumor expression of the anthracyclines remains unknown-there is now evidence that the relationship of the anthracyclines to the DNA (possibly requiring enzymatic cooperation) and to the membranes, with neither event requiring redox chemistry, may comprise the core of the antitumor effects. The adventitious expression of the redox activity under either aerobic conditions (in which circumstances molecular oxygen is reduced) or anaerobic conditions (in which circumstances potentially reactive aglycone tautomers are obtained) is therefore thought to contribute more strongly to the host toxicity. Yet little remains proven, and the understanding of the intrinsic chemical competence can do little more than lightly define the boundaries within which are found these and numerous other working hypotheses.

show abstract

Membrane alterations associated with progressive adriamycin resistance

Cited by 62 publications

References 23 publications

Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Effect of polyunsaturated fatty acids on the drug sensitivity of human tumour cell lines resistant to either cisplatin or doxorubicin

A chemical perspective on the anthracycline antitumor antibiotics.

Contact Info

Product

Resources

About