AU-1 from Agavaceae plants downregulates the expression of glycolytic enzyme phosphoglycerate mutase.

The spirostanol saponin AU-1 from Agavaceae plants stimulates the expression of the glycolytic enzyme phosphoglycerate mutase (PGAM) in ACHN cells. We hypothesized that this may arise from the downregulation of the NAD-dependent deacetylase SIRT1. In this article, we showed that, unlike in renal adenocarcinoma cells, AU-1 does not affect the expression of SIRT1 in the normal renal cell-derived cell line HK-2. Consistent with the lack of a downregulation of SIRT1, AU-1 did not upregulate, but rather decreased PGAM expression. Moreover, AU-1 inhibited the increase in PGAM levels that results from the knock-down of SIRT1. Our results suggest that AU-1 may prevent carcinogenesis caused by increased cellular PGAM.