J. Cornelissen et al., METAIODOBENZYLGUANIDINE INHIBITS COMPLEX-I AND COMPLEX-III OF THE RESPIRATORY-CHAIN IN THE HUMAN CELL-LINE MOLT-4, Biochemical pharmacology, 49(4), 1995, pp. 471-477
In this paper we report the effects of meta-iodobenzylguanidine (MIBG)
, a structural analogue of norepinephrine, on cell proliferation and s
everal parameters related to mitochondrial respiration in Molt-4 cells
. In micromolar concentrations, MIBG completely inhibited the prolifer
ation of Molt-4 cells. In intact Molt-4 cells, a progressive increase
in the lactate to pyruvate ratio was observed after incubation of thes
e cells with glucose and increasing concentrations of MIBG. In Molt-4
cells permeabilized with digitonin, MIBG inhibited mitochondrial ATP s
ynthesis when malate was used as a substrate. Succinate-driven synthes
is of ATP was also inhibited by MIBG, although higher concentrations w
ere required. These results indicate that apart from inhibition of com
plex I, MIBG inhibits at least one other complex of the respiratory ch
ain. Measurement of the activities of the individual enzyme complexes
in the presence of MIBG revealed that complex III is the other enzyme
complex susceptible to inhibition by MIBG. Although maximal inhibition
of ATP synthesis was observed at a concentration of 10 mu M, maximal
inhibition of cell proliferation was observed at a concentration of 50
mu M of MIBG. This suggests that MIBG also influences other cellular
processes apart from mitochondrial oxidative phosphorylation, resultin
g in additional inhibition of cell proliferation.