Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced byN-methyl-N?-nitro-N-nitrosoguanidine in Wistar rats

Abstract

The effects of prolonged administration of genistein, a tyrosine‐kinase inhibitor, on sodium‐chloride‐enhanced induction of gastric carcinogenesis induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, and the labeling and apoptotic indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were fed chow pellets containing 10% sodium chloride and were given s.c. injections of genistein at dosages of 15 mg/kg or 30 mg/kg body weight every other day. In week 52, the incidence of gastric cancers was significantly greater in rats fed sodium chloride than in untreated control rats. Prolonged administration of genistein at a dosage of 30 mg/kg, but not 15 mg/kg, body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride. Genistein at the higher dose significantly decreased the labeling index and vessel counts of the antral mucosa and the gastric cancers (which were increased by treatment with sodium chloride) and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodium chloride). These findings suggest that genistein attenuates gastric carcinogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric cancers. Int. J. Cancer 80:396–399, 1999. © 1999 Wiley‐Liss, Inc.

Upregulation of KIF20A correlates with poor prognosis in gastric cancer

“…The concentration of genistein that had cell growth inhibition effect was in a micromolar range as its IC 50 value was about 20 μM ( Figure 4B ). Although numerous reports verified that there were no toxic effects exerted by genistein to normal cells, 12 , 17 – 20 its dose for inhibition tumor cell growth (nearly 100 μmol range) was relatively high and had potential risk in clinical application. So, we thought whether combining it with the first-line chemotherapy drugs in GC could enhance their antitumor effects.…”

“…Genistein, one of the most important isoflavones, has been shown to have anticancer effects in many cancers, without exerting toxic effects on normal cells. 12 , 17 – 20 In GC, Yan et al 12 showed that genistein can induce mitotic arrest by downregulation of KIF20A, which inhibited cell viability and induced G2/M arrest. Therefore, genistein might be a potential drug targeting KIF20A in GC.…”

Dietary isoflavones and gastric cancer: A brief review of current studies

“…Hence, genistein is able to inhibit the autophosphorylation of these receptors; therefore, the proliferation or angiogenesis in these tumor cells is inhibited. [ 33 ]…”

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

“…On the other hand, genistein can be chemically synthesized using conventional microwave ovens [174,176] or it can be biotechnologically synthesized by germinating the soybean seeds and enhancing its genistein content or by genetically manipulating non-legume crop such as rice (i.e., transgenic rice with high genistein content) [174]. Genistein exerts its anticancer effects by inducing apoptosis, decreasing proliferation, and inhibiting angiogenesis, as well as metastasis, which was illustrated in decreased tumor growth and development in hepatocellular cancer models of nude mice [180] and Wistar rats [181], as well as in gastric cancer model of Wistar rats [182]. Genistein role in prostate cancer was extensively studied in vivo in different animal models, such as Lobund-Wistar rat, (which is a unique rat model that spontaneously develops metastastic prostate cancer in 30% of its population), and in SCID mice transplanted with human prostate carcinoma cells (LNCaP, PC3, and DU-145).…”