Impaired mitochondrial respiration and stimulated glycolysis by m-iodobenzylguanidine (mibg)
✍ Scribed by Cornelia Loesberg; Henny Van Rooij; Willem J. Nooijen; Alfred J. Meijer; Lou A. Smets
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- French
- Weight
- 651 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
m-lodobenzylguanidine (MIBG) is a functional analogue of the neurotransmitter norepinephrine. Radio-iodinated l 3 I l - MlBG is used clinically as a tumor-targeted radiopharmaceutical agent in the diagnosis and treatment of adrenergic tumors. Native MlBG 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 MlBG was investigated on isolated rat liver mitochondria and on various tumor cell lines (human neuroblastoma SK-N-SH, mouse neuroblastoma N, E I I5 and mouse lymphosarcoma S49). Results revealed that MIBG inhibits respiration of isolated liver mitochondria at complex I of the respiratory chain, without affecting F, 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 MlBG was proportional to drug-induced alterations in glucose metabolism.