Rapid tumor growth is dependent on the capability of tumor blood vessels and
glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of
many solid tumors, and it essentially happens when the growth of the tumor exceeds the
concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription
factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids,
widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing
broadspectrum pharmacological activities, including their potentiality as anticancer
agents. Due to their low toxicity, intense efforts have been made for investigating natural
flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy
during the past few decades. In this review, we sum up the findings concerning the inhibition
of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and
glycolytic multi-target inhibitors with HIF-1α as one of the targets.
Keywords: HIF-1α, natural flavonoids, anticancer, inhibition, signaling pathway, hypoxia situation.
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