Regulation of hypoxia-inducible factor-1α and vascular endothelial growth factor signaling by plant flavonoids

Discovery of novel drugs that are able to prevent angiogenesis is a fast growing branch of cancer research. Current approaches to cancer chemotherapy include the use of alkylating agents, antimetabolites, antitumor antibiotics, platinum analogs and drugs derived from natural compounds. However, most of the currently used chemotherapeutic drugs have adverse side effects on normal healthy cells. In addition to the classical targets of cancer chemotherapy, prevention of angiogenesis through the regulation of indigenous angiogenic factors is a leading approach of developing selective novel anticancer drugs. Because of their low toxicity, there is increasing interest in exploring specific dietary phytochemicals as possible antiangiogenic agents. In this mini-review, selected flavonoids (e.g., apigenin, luteolin, quercetin and epigallocatechin-3- gallate, which are a group of plant polyphenols) that are able to regulate angiogenesis in in vitro and in vivo systems are discussed in the light of their potential to be exploited as novel anticancer drugs.