Previous attempts to use
tumor energy metabolism as a target for
antineoplastic therapy have used single agents aimed at inhibiting either glycolysis or oxidative phosphorylation. Since most
tumor cells use both pathways for energy production, this approach is unlikely to succeed. The aim of this study was to simultaneously manipulate both sources of intracellular
ATP to achieve more selective control of
tumor growth.
Rhodamine 6G (R6G) is a
fluorochrome mitochondrial
dye which inhibits oxidative phosphorylation.
3-Mercaptopicolinic acid inhibits gluconeogenesis and is a potent
hypoglycemic agent in the fasting state. Dose-response relationships were established for R6G and
3-mercaptopicolinic acid, and a nontoxic dose of the compounds was selected for subsequent experiments. Thereafter, groups of rats (n = 7 per group) underwent s.c. implantation of Walker 256
carcinosarcoma. Following a 24-h fast each group received either saline, R6G (0.8 mg/kg),
3-mercaptopicolinic acid (40 mg/kg), or the combination given i.p. Seven days after
tumor implantation animals were sacrificed, and
tumors were exercised and weighed. Administration of R6G during a period of
hypoglycemia significantly reduced the
tumor growth rate when compared to control experiments (3.6 +/- 0.3 g cf. 7.1 +/- 0.7 g, mean +/- SE; P less than 0.05). In contrast, neither R6G nor the period of
hypoglycemia alone significantly affected
tumor growth. These results suggest that simultaneous manipulation of oxidative phosphorylation and glycolysis may be used to selectively inhibit
tumor growth in vivo.