TY - JOUR
T1 - Glycolysis in P-glycoprotein-overexpressing human tumor cell lines Effects of resistance-modifying agents
AU - Broxterman, Henricus J.
AU - Pinedo, Herbert M.
AU - Kuiper, Catharina M.
AU - Schuurhuis, Gerrit J.
AU - Lankelma, Jan
PY - 1989/4/24
Y1 - 1989/4/24
N2 - We show that drugs, such as verapamil, which reverse multidrug resistance (MDR), in P-glycoprotein-overexpressing tumor cells, increased the rate of lactate production in four human MDR cell lines, but not in the parent, sensitive cell lines. The effect on glycolytic rate was maximal at a medium concentration of 2 μM verapamil. The glycolytic rate in sensitive (A2780) and MDR (2780AD) cells showed the same pH dependence, but the effect of verapamil was seen only in 2780AD cells at all pH values investigated (6.6, 7.4 and 8.2). A series of drugs such as nigericin, oligomycin, amiloride and monensin had similar effects in the two cells. Phorbol myristate acetate increased lactate formation in neither cell line. Verapamil induced an extra amount of ATP consumption in P-glycoprotein-expressing 2780AD cells of approx. 25 pmol/s per 106 cells, which was estimated to be about 10% of cellular energy turnover.
AB - We show that drugs, such as verapamil, which reverse multidrug resistance (MDR), in P-glycoprotein-overexpressing tumor cells, increased the rate of lactate production in four human MDR cell lines, but not in the parent, sensitive cell lines. The effect on glycolytic rate was maximal at a medium concentration of 2 μM verapamil. The glycolytic rate in sensitive (A2780) and MDR (2780AD) cells showed the same pH dependence, but the effect of verapamil was seen only in 2780AD cells at all pH values investigated (6.6, 7.4 and 8.2). A series of drugs such as nigericin, oligomycin, amiloride and monensin had similar effects in the two cells. Phorbol myristate acetate increased lactate formation in neither cell line. Verapamil induced an extra amount of ATP consumption in P-glycoprotein-expressing 2780AD cells of approx. 25 pmol/s per 106 cells, which was estimated to be about 10% of cellular energy turnover.
KW - Glycolysis
KW - Glycoprotein, P-
KW - Multidrug resistance
KW - Verapamil
UR - http://www.scopus.com/inward/record.url?scp=0024523052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024523052&partnerID=8YFLogxK
U2 - 10.1016/0014-5793(89)81380-8
DO - 10.1016/0014-5793(89)81380-8
M3 - Article
C2 - 2565823
AN - SCOPUS:0024523052
SN - 0014-5793
VL - 247
SP - 405
EP - 410
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -