Molecular Targets of Genistein and Its Related Flavonoids to Exert Anticancer Effects

Abstract

Increased health awareness among the public has highlighted the health benefits of dietary supplements including flavonoids. As flavonoids target several critical factors to exert a variety of biological effects, studies to identify their target-specific effects have been conducted. Herein, we discuss the basic structures of flavonoids and their anticancer activities in relation to the specific biological targets acted upon by these flavonoids. Flavonoids target several signaling pathways involved in apoptosis, cell cycle arrest, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT kinase, and metastasis. Polo-like kinase 1 (PLK1) has been recognized as a valuable target in cancer treatment due to the prognostic implication of PLK1 in cancer patients and its clinical relevance between the overexpression of PLK1 and the reduced survival rates of several carcinoma patients. Recent studies suggest that several flavonoids, including genistein directly inhibit PLK1 inhibitory activity. Later, we focus on the anticancer effects of genistein through inhibition of PLK1.

Keywords: PLK1; anticancer; flavonoid; genistein.

Figure 1

Structures of basic flavonoids and selected structures. Two main classes of flavonoids, Flavonoid (flavones, flavanones, and flavonols), and Isoflavonoid, are presented and additionally, modified flavonoids are frequently found in dietary and medicinal plants are described.

Figure 2

Action mechanisms of genistein to exert anticancer effects. Genistein exhibits anticancer effects by inhibiting the activities of receptor tyrosine kinase including EGFR and serine/threonine cell cycle regulatory kinases such as PLK1 and CDK1. Genistein also suppresses the transcriptional expression of PLK1. It is also considered as a tissue-specific hormone modulator.