Abstract

The effect of ketone bodies on the growth, in culture, of transformed lymphoblasts (Raji cells) was investigated. Cell growth was inhibited and this effect was reversible, non-toxic, and proportional to the concentration of D-beta-hydroxybutyrate up to 20mM. The total glucose utilisation and the total lactate production were reduced in proportion to the inhibition of cell proliferation. D-beta-hydroxybutyrate was not metabolised by the cells. Other glycolytic inhibitors and chemical analogues of D-beta-hydroxybutyrate either did not inhibit or proved to be too toxic for cell growth. D-beta-hydroxybutyrate also inhibited the growth of rabbit kidney (RK13), HeLa, mouse melanoma (B16), fibroblast and trypsin-dispersed human thyroid and beef testis cells. Moreover, in vivo dietary-induced ketosis reduced the number of B16 melanoma deposits in the lungs of C57BL/6 mice by two-thirds. The significance of these results in the clinical management of cancer cachexia is discussed.