Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

Abstract

Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 μM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer.

Polyphenols delivery by polymeric materials: challenges in cancer treatment

“…Acting on the same signaling pathway in prostate cancer, genistein was shown to suppress prostatosphere and colony formation in vitro and tumorigenicity in vivo (Zhang et al, 2012a). In gastric cancer cells, genistein was reducing the chemoresistance of CSCs to 5-FU and CP by targeting ABCG2 expression and ERK 1/2 activity (Huang et al, 2014).…”

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter

“…5C). Only one other study has reported a significant decrease in ABCG2 mRNA expression after an in vitro genistein exposure (15 mM, 24 hours, gastric cancer cells, MGC803) (Huang et al, 2014), whereas many others detected no change in BCRP mRNA and/or protein expression in other cell types (Imai et al, 2004;Ebert et al, 2007;Arias et al, 2014).…”

Understanding genistein in cancer: The “good” and the “bad” effects: A review

“…Activation of the signaling cascade by ERK 1/2 occurs commonly in many types of cancer. Studies on gastric cancer cells suggest that genistein enhances the chemosensitivity by suppressing the activity of ERK 1/2 (Huang, Wan, Luo, Huang, & Luo, 2014).…”