Soy and breast cancer: focus on angiogenesis

Abstract

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

Keywords: angiogenesis; breast cancer; galectins; genistein; soy.

Figure 1

Molecular targets of genistein on endothelial (EC) and cancer (CC) cells. Akt-protein kinase B; bFGF—basic fibroblast growth factor; COX-2—cyclooxygenase-2; EGF—fibroblast growth factor; ERK—extracellular signal-regulated kinases; HIF—hypoxia inducible factor; IGF—insulin-like growth factor; JNK-c—Jun N-terminal kinases; MAPK—mitogen-activated protein kinase; MAPKAPK2—MAP kinase activated protein kinase 2; MMP-matrix metalloproteinase; NF-κB—nuclear factor κB; PDGF—platelet-derived growth factor; TF—tissue factor; TNF-α—tumor necrosis factors α; uPA—urokinase plasminogen activator; VEGF—vascular endothelial growth factor; VEGFR1—receptor for vascular endothelial growth factor 1.