Chlorogenic acid modulates hypoxia response of Hep3B cells

Coffee is the most widely consumed beverage around the world, and it contains many compounds that have beneficial effects on human health. Chlorogenic acid (CGA), the most abundant polyphenol in coffee, has been reported to inhibit cancer cell growth and has a beneficial effect on ameliorating aging-related diseases. We found that CGA decreased HIF-1α levels in human hepatoma cell line Hep3B under hypoxic conditions (O₂ = 1%) in a dose-dependent manner, thereby decreasing the expression of its downstream targets EPO and VEGF. However, similar effects were not found in the presence of 100 μM 2,2′-dipyridyl. Further studies showed that the lysosomal protease inhibitor NH₄Cl inhibited the decrease in HIF-1α levels, whereas the proteasome inhibitor MG132 did not, indicating that CGA requires lysosomal protease to affect the hypoxia response.