Glutathione S-Transferase Does Not Play a Role in
Multidrug Resistance of L1210/VCR Cell Line
V. BOHÁČOVÁ, J. KVAČKAJOVÁ1,
M. BARANČÍK1, Z. DROBNÁ1,
A. BREIER
Institute of Molecular Physiology and Genetics and 1Institute
for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic
Received March 22, 1999
Accepted February 9, 2000
Summary
Multidrug resistance of cancer cells is often accompanied by
the (over)expression of integral plasma membrane P-glycoprotein, an ATP-dependent transport pump for diverse unrelated compounds.
The glutathione detoxification system represents another mechanism that may be
involved in multidrug resistance. In the multidrug-resistant L1210/VCR cell line
obtained by long-term adaptation of parental L1210 cells to vincristine, an
increased expression of P-glycoprotein has previously been established. In this
paper, we investigated if the glutathione detoxification system is also
involved in the multidrug resistance of these cells. L1210/VCR cells with
resistance induced by adaptation to vincristine were also found to be
cross-resistant to vinblastine, actinomycin D, mitomycin C, doxorubicin and
cyclophosphamide. The resistance of the above cells to vincristine and
doxorubicin was accompanied by a depression of drug accumulation (which has not
yet been established for other drug). L1210/VCR cells are able to survive better
than sensitive cells under conditions when glutathione was depleted by L-buthionine
sulfoximine. Nevertheless, L-buthionine sulfoximine did not influence the resistance of L1210/VCR cells to
vincristine. Moreover, the presence of sublethal concentrations of cytostatics
neither changed the IC50 value of resistant cells to L-buthionine
sulfoximine nor the cytoplasmic activity of glutathione S-transferase, the
crucial enzyme of glutathione detoxification system. All the above findings
indicate that the glutathione detoxification system is not involved in the
mechanisms that ensure the multidrug resistance phenotype of L1210/VCR cells.
Key words
P-glycoprotein · Multidrug resistance ·
L1210 leukemic cell lines · Cytostatic drugs
Reprint requests
A. Breier, Institute of Molecular Physiology and Genetics,
Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovak Republic,
e-mail: usrdtylo@savba.sk
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