Genistein

Genistein is a highly specific inhibitor of tyrosine kinase with IC50 value of ~ 8 μM [1].

Tyrosine protein kinase activities are known to be associated with oncogene products of the retroviral “src” gene family and with various cellular growth factor receptors including epidermal growth factor (EGF), platelet derived growth factor (PDGF), insulin and insulin-like growth factors, which play a key role in tumorogenesis. Thus, inhibitors of protein tyrosine kinase activity might represent a new class of antitumor agents [2].

In NIH-3T3 cells, Genistein blocked the mitogenic effect mediated by EGF with IC50 value of 12 μM or by insulin with IC50 value of 19 μM. In NIH-3T3 cells treated with EGF, Genistein partially prevented the increase of S6 kinase activity at 6 μM, with the maximal effect observed at 15 μM [2].

In a chemically (N-methylnitrosourea) induced prostate cancer rat model, Genistein (0, 25 or 250 mg/kg, p.o.) in the diet dose-dependently inhibited the development of invasive adenocarcinomas. In a transgenic mouse model that spontaneously developed prostate cancer, Genistein (0, 100, 250 or 500 mg/kg, p.o.) in the diet lowered the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner [3].

References:

[1]. Baltuch G H, Yong V W. Signal transduction for proliferation of glioma cells in vitro occurs predominantly through a protein kinase C-mediated pathway. Brain Research, 1996, 710(1-2): 143-149.

[2]. Linassier C, Pierre M, Le Pecq J B, et al. Mechanisms of action in NIH-3T3 cells of genistein, an inhibitor of EGF receptor tyrosine kinase activity. Biochemical Pharmacology, 1990, 39(1): 187-193.

[3]. Lamartiniere C A, Cotroneo M S, Fritz W A, et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. Journal of Nutrition, 2002, 132(3): 552S-558S.