Increase in hypoxia-inducible factor-1α (HIF-1α) expression is caused by some essential trace elements such as vanadium and cobalt even under normoxic conditions. The mechanism of HIF-1α activation caused by vanadium is not documented well whereas several authors proposed that by cobalt. When HEK293 cells were treated with 100 μM sodium orthovanadate, HIF-1α expression increased within 6 to 12 hours. The increase was suppressed by HIF-1α-specific inhibitors, YC-1 for the metal-related oxygen sensing pathway, and 17-AAG for the Hsp90-dependent pathway. The results suggest that orthovanadate increases HIF-1α expression via both oxygen-dependent and -independent pathways.