Roxarsone (Rox) is
an organic arsenic compound used as a feed additive
to promote animal growth. The release of Rox into the environment
poses risks to human health. Rox demonstrated tumor-promoting and
proangiogenic effects in xenograft models. Increasing studies revealed
the tight relationship among angiogenesis, carcinogenesis, tumorigenesis,
and glycolysis. Glycolysis, via hypoxia-inducible factor-1α
(HIF-1α), controls vascular endothelial cell (VEC) growth. To
date, there has been no literature report on the effect of Rox on
HIF-1α-dependent glycolysis. Herein, we report that Rox promoted
glycolysis in rat VECs, as shown by the increased adenosine triphosphate
production, the lactic acid release, the activity and content of aldolase
(ALD), and the expression levels of ALD A and glucose transporter
1 (GLUT1). Rox also increased the cellular levels of HIF-1α.
Treatment with the HIF-1α inhibitor YC-1 reversed Rox-increased
ALD A and GLUT1 levels and attenuated Rox-induced VEC viability, suggesting
that Rox-induced HIF-1α contributes to the glycolytic and angiogenic
effects of Rox. Rox also promoted tumor growth and angiogenesis and
increased the levels of ALD A, GLUT1, and HIF-1α in the tumor
tissue of a mouse xenograft model, whereas these effects were abolished
using YC-1. Our findings indicated that Rox induces HIF-1α in
VECs to promote glycolysis and angiogenesis thus enhancing the tumor
growth.