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.
Highlights
Breast cancer is the second most frequently diagnosed cancer and the leading cause of death among woman in developed countries, accounting for 22% of new cases each year [1]
5α-reductase, protein histidine kinase, and cyclin-dependent kinases [32,33,34,35]; (ii) decrease the signaling pathways associated with the growth of cancer cells (e.g., nuclear factor κB (NF-κB), Akt, mitogen-activated protein kinase (MAPKs)); and (iii) apoptosis induction [36]
Data bevacizumab was approved by the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of HER2-negative metastatic breast cancer when administered in combination with chemotherapy
Summary
Breast cancer is the second most frequently diagnosed cancer and the leading cause of death among woman in developed countries, accounting for 22% of new cases each year [1]. Several epidemiologic studies evaluating the relation between soy intake and breast cancer incidence has been conducted in the world [10,11,12,13,14]. Most breast cancers are hormone-receptor-positive [22] Soy phytoestrogens, such as genistein, daidzein, and glycitein, are isoflavonoids closely related to human 17β-estradiol [23], but with lower estrogenic activity [24]. Genistein has been identified as the predominant isoflavone in soybean It possesses biphasic effect on estrogen receptor (ER) positive breast cancer cells. Apart from its estrogenic/antiestrogenic activity, genistein inhibits growth of hormone non-dependent cancer cells [27,28]. Genistein and other soy isoflavonoids exhibit multiple effects on the human malignant cells and modulate selected steps of angiogenesis
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