TY - JOUR
T1 - Enhancement of doxorubicin content by the antitumor drug lonidamine in resistant ehrlich ascites tumor cells through modulation of energy metabolism
AU - Floridi, Aristide
AU - Bruno, Tiziana
AU - Miccadei, Stefania
AU - Fanciulli, Maurizio
AU - Federico, Antonio
AU - Paggi, Marco G.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - The effect of the antitumor drug lonidamine (LND) on respiration, aerobic glycolysis, adenylate pool, doxorubicin (DOX) uptake, and efflux in DOX-resistant and DOX-sensitive Ehrlich tumor cells was investigated. The results may be summarized as follows: 1) In both types of cells, LND inhibited both respiration and glycolysis in a dose-dependent manner and lowered the ATP concentration. The effect was more marked in cells incubated in glucose-free medium; 2) LND raised, to a remarkable extent, the intracellular content of DOX in resistant and sensitive cells respiring on endogenous substrates because of reduced ATP availability, whereas in glucose-supplemented medium, where both respiration and glycolysis contributed to ATP synthesis, the increase was lower; and 3) when LND was added to DOX-loaded cells, it failed to significantly inhibit DOX efflux because of time-dependent phenomena. These findings indicated that LND, a drug currently employed in tumor therapy, might also be useful in reducing or overcoming multidrug resistance (MDR) of those cells with a reduced ability to accumulate and retain antitumor drugs. Copyright (C) 1998 Elsevier Science Inc.
AB - The effect of the antitumor drug lonidamine (LND) on respiration, aerobic glycolysis, adenylate pool, doxorubicin (DOX) uptake, and efflux in DOX-resistant and DOX-sensitive Ehrlich tumor cells was investigated. The results may be summarized as follows: 1) In both types of cells, LND inhibited both respiration and glycolysis in a dose-dependent manner and lowered the ATP concentration. The effect was more marked in cells incubated in glucose-free medium; 2) LND raised, to a remarkable extent, the intracellular content of DOX in resistant and sensitive cells respiring on endogenous substrates because of reduced ATP availability, whereas in glucose-supplemented medium, where both respiration and glycolysis contributed to ATP synthesis, the increase was lower; and 3) when LND was added to DOX-loaded cells, it failed to significantly inhibit DOX efflux because of time-dependent phenomena. These findings indicated that LND, a drug currently employed in tumor therapy, might also be useful in reducing or overcoming multidrug resistance (MDR) of those cells with a reduced ability to accumulate and retain antitumor drugs. Copyright (C) 1998 Elsevier Science Inc.
KW - Doxorubicin
KW - Ehrlich tumor cells
KW - Energy metabolism
KW - Ionidamine
KW - Multidrug resistance
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UR - http://www.scopus.com/inward/citedby.url?scp=0032190467&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(98)00054-9
DO - 10.1016/S0006-2952(98)00054-9
M3 - Article
C2 - 9774146
AN - SCOPUS:0032190467
VL - 56
SP - 841
EP - 849
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 7
ER -