Apigenin inhibits tumor angiogenesis through decreasing HIF-1  and VEGF expression

Abstract

Apigenin is a non-toxic dietary flavonoid with anti-tumor properties. We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition. However, the effect of apigenin in angiogenesis remains to be elucidated. Angiogenesis is the formation of new blood vessels and is required for tumor growth and metastasis. In this study, we showed that apigenin-inhibited expression of HIF-1 and VEGF in different cancer cells under both normoxic and hypoxic conditions. We demonstrated that apigenin significantly inhibited tumor angiogenesis in vivo, by using both the chicken chorioallantoic membrane and Matrigel plug assays. The inhibition of tumor angiogenesis was associated with the decrease of HIF-1 and VEGF in tumor tissues. Taken together, our results show that apigenin suppresses tumor angiogenesis through HIF-1 and VEGF expression.

A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

“…This result may be due to chance, based on the absence of a monotonic trend across quintiles of intake and the lack of a significant association with continuous intake of apigenin, in conjunction with biologic data that do not support a positive association. 20,21 However, this should be evaluated in future studies, to rule out the possibility of a harmful association with apigenin or specific foods that contribute to apigenin intake.…”

“…54 Finally, evidence from in vitro studies of human ovarian cancer cell lines suggests that certain flavonoids can inhibit tumor growth and angiogenesis, interrupt the cell cycle, and induce apoptosis, all of which may be relevant mechanisms for an inverse association between flavonoid intake and ovarian cancer. 20,21,[55][56][57] Although the flavonoid concentrations used in these experimental studies generally exceeded the levels obtainable with typical dietary intake, there was some overlap with the plasma levels of flavonoids observed in feeding studies in humans. For example, the quercetin plasma concentrations observed in several studies where participants ingested 20-100 mg of quercetin, levels comparable with the intakes for women in quintiles 4 and 5 of our study population, were within the range of the quercetin concentrations associated with decreased proliferation of ovarian cancer cells in a study by Scambia et al [57][58][59] This analysis is the largest and most comprehensive assessment of the association between total dietary flavonoid intake and ovarian cancer risk to date.…”

Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells

“…For example, Apigenin, a natural product, inhibits tumor angiogenesis by decreasing HIF-1α and VEGF expression. 30 Similarly, Thymoquinone, a phytochemical compound found in the plant Nigella sativa, inhibits tumor angiogenesis and tumor growth by suppressing extracellular signal-regulated kinase signaling pathways. 31 Until now, although antiangiogenic molecules dominantly target endothelial cells and exhibit effective control of tumor angiogenesis, the finding of a natural product-derived single compound to control the tumor mass via the marked delay of tumor angiogenesis, particularly through the modulation of stem/progenitor cells bioactivities, are largely unknown.…”

Hot-water Extract of Rubus Coreanus Miquel Suppresses VEGF-induced Angiogenesis

“…Many anti-angio- to serious side effects [28]. Therefore, there has been a renewed interest in identifying VEGF inhibitors from natural herbal sources, given the advantage of their proven safety for human use [5,7,13]. Additionally, certain plant-derived diets containing phytochemicals have been implicated in the prevention of cancer development and progression [2,24,50,56].…”