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Impaired mitochondrial respiration and stimulated glycolysis by m ‐iodobenzylguanidine (mibg)
Author(s) -
Loesberg Cornelia,
Rooij Henny Van,
Nooijen Willem J.,
Meijer Alfred J.,
Smets Lou A.
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910460223
Subject(s) - neuroblastoma , glycolysis , mitochondrion , endocrinology , intracellular , respiration , medicine , cytotoxicity , biology , metabolism , respiratory chain , lactic acid , cell culture , biochemistry , chemistry , in vitro , genetics , botany , bacteria
m ‐lodobenzylguanidine (MIBG) is a functional analogue of the neurotransmitter norepinephrine. Radio‐iodinated 131 I‐MIBG is used clinically as a tumor‐targeted radiopharmaceutical agent in the diagnosis and treatment of adrenergic tumors. Native MIBG has previously been demonstrated to be cytotoxic in cultured cells and to produce anti‐tumor responses in animals when non‐toxic schedules are used. In this study the effect of MIBG was investigated on isolated rat liver mitochondria and on various tumor cell lines (human neuroblastoma SK‐N‐SH, mouse neuroblastoma N 1 E115 and mouse lymphosarcoma S49). Results revealed that MIBG inhibits respiration of isolated liver mitochondria at complex I of the respiratory chain, without affecting F 1 ATP‐ase. In cell lines, impairment of the mitochondrial respiration was evident from reduced oxygen consumption and decreased intracellular ATP levels. In response to this effect, the glycolytic flux was stimulated as shown by increased glucose consumption and lactic acid production. Cytotoxicity of MIBG was proportional to drug‐induced alterations in glucose metabolism.