Abstract
Esophageal carcinoma (EsC) is a clinically challenging neoplastic disease. Genistein, a natural isoflavone product, has anti-tumor properties. Through in vitro and in vivo studies, we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner. In addition, genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner. Furthermore, high concentrations of genistein have no adverse effect on normal esophageal epithelial cells. Mechanistically, genistein treatment strikingly reduced the expression of cell cycle-associated genes, and up-regulated the expression of cell apoptosis-related genes in EsC cells. Additionally, genistein dramatically decreased epidermal growth factor receptor (EGFR) expression and attenuated its down-stream signaling molecules STAT3, MDM2, Akt and JAK1/2 phosphorylation, resulting in inhibited nuclear translocation of STAT3 and MDM2, thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways. In xenograft nude mice, genistein administration strikingly impaired tumor growth in a dose-dependent manner. Moreover, similar disturbances in molecular mechanisms were observed in vivo. Taken together, genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression, leading to cell apoptosis, cell cycle arrest, and proliferation inhibition in EsC cells. Our findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC.
Highlights
Esophageal carcinoma (EsC) is a malignant tumor originating from the mucosal epithelium of the esophagus
Genistein suppresses the proliferation of esophageal cancer cells
We found that genistein induced apoptosis (Figure 2A–2F, P
Summary
Esophageal carcinoma (EsC) is a malignant tumor originating from the mucosal epithelium of the esophagus. In 2015, there were approximately 477,900 new cases of esophageal cancer and 37,500 related deaths in China, accounting for 11.13% and 13.33% of the tumor incidence and mortality, respectively [1]. The www.aging-us.com prevention and treatment of EsC in China is a great challenge. Because of the relatively insidious onset of EsC and the lack of early specific symptoms, most patients are diagnosed at a mid-term or advanced stage. Chemotherapy is the standard therapy for patients with advanced EsC who cannot receive surgical treatment, and the therapeutic effect depends on the sensitivity of the tumor cells to the chemotherapy drugs. Chemo-resistant tumors are common, resulting in the failure of chemotherapy [4, 5]
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