The Growth Response to Beta-Hydroxybutyrate in SH-SY5Y Neuroblastoma Cells is Suppressed by Glucose and Pyruvate Supplementation

Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system and is commonly studied using the SH-SY5Y cell line. Its neoplastic and neurodevelopmental manifestations are characterised by a high glucose demand which maintains its high proliferative capacity. This metabolic phenotype may be utilised in dietary therapies such as the ketone diet which alter substrate availability and thus starve NB cells of their preferred biosynthetic requirements. However, the effects of ketone metabolism on cancer growth remain poorly understood due to the involvement of other metabolic substrates in experimental paradigms and complexities underlying the Warburg effect. We investigated how the primary ketone body beta-hydroxybutyrate (βOHB) affects the growth of SH-SY5Y NB cells in the presence or absence of culture metabolic substrates. We demonstrated that while glucose deprivation reduced the growth and viability of SH-SY5Y cells, they proliferated and were initially unaffected by the addition of βOHB. However, a growth response to βOHB was subsequently revealed in media containing low levels of glucose, as well as in glucose and pyruvate deprived conditions. These data shed light on the roles of metabolic substrate availability as key determinants of the responses of SH-SY5Y NB cells to ketone supplementation.