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Mitochondria-bound hexokinase as target for therapy of malignant gliomas

✍ Scribed by Stéphane Oudard; Florence Poirson; Laurent Miccoli; Yveline Bourgeois; Anne Vassault; Michel Poisson; Henri Magdelénat; Bernard Dutrillaux; Marie-France Poupon

Publisher
John Wiley and Sons
Year
1995
Tongue
French
Weight
806 KB
Volume
62
Category
Article
ISSN
0020-7136

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✦ Synopsis

Hexokinase plays an important role in glucose-utilizing tissues like normal brain and cancers. In these tissues, hexokinase (HK) is mainly bound to mitochondria (mHK). Our objectives were to evaluate total HK (tHK) activity and mHK fraction in gliomas and to determine whether mHK binding could be targeted for therapy. Tumors were obtained from 26 patients and I 3 were xenografted. HK. lactate and ATP were measured in cytosol and mitochondria extracts. The tHK expressed in mU/mg protein were I47 f I9 and 78 2 12, in fresh gliomas and xenografts, respectively, and of 489 in the normal brain. The mHK fraction was 76% in normal brain, 74 f 4% in fresh tumors and 53 -c 6% in xenografts. Lactate/mHK ratios were higher in gliomas than in normal brain. The ATP was I0,52 & 3 I and I9 f 8 nmol/mg protein in normal brain, xenografts and fresh gliomas respectively. Loss of one copy of chromosome 10 which

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