Solid tumors that occur in colorectal cancer are known to grow in hypoxic environments and hypoxia-inducible factor-1 (HIF-1),which promotes angiogenesis,has a critical role in cellular responses to hypoxia.Inhibition of tumor angiogenesis is looked upon as a promising strategy for anticancer chemotherapy as various kinds of anti-angiogenic agents are currently in preclinical development or entering clinical trials.However,signaling pathways related to angiogenesis are usually redundant with crosstalk between these pathways that form a complicated and robust network which is regulated by several compensatory mechanisms.Traditional Chinese medicine (TCM),has been used clinically to treat various kinds of diseases for thousands of years.Pien Tze Huang (PZH) is a well-known TCM formula that has been used as an anticancer therapeutic in China and Southeast Asia for centuries.The mechanism through which PZH effectively stops tumor growth has not been elucidated.In the present study,we found PZH to significantly decrease hypoxia-induced HIF-1α protein levels in HCT-8 colorectal carcinoma cells.Moreover,PZH suppressed transcriptional activity of HIF-1α during hypoxia leading to decreased VEGF-A expression,blocked hypoxia-stimulated migration and diminished angiogenesis.The down-regulation of HIF-1α and VEGF-A in response to PZH during hypoxia was also present in HUVECs.These findings suggest PZH inhibits tumor angiogenesis via suppression of HIF-1α/VEGF-A signaling.