Rhizoma Paridis Saponins Suppresses Tumor Growth in a Rat Model of N-Nitrosomethylbenzylamine-Induced Esophageal Cancer by Inhibiting Cyclooxygenases-2 Pathway

Abstract

Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1mg/kg) for 10 weeks. RPS (350 mg/kg or 100mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.

Carcinogenesis: Failure of resolution of inflammation?

“…A frequent model of colon carcinogenesis is induced by azoxymethane (AOM) and promoted with dextran sodium sulfate (DSS) ( Hattori et al, 2019 ; Yamaguchi, Takai, Hosono, & Seki, 2014 ; Yang et al, 2018 ). N -nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in esophagus is a model of human esophageal squamous cell carcinoma used for investigations of chemical carcinogenesis ( Carlton et al, 2002 ; Yan et al, 2015 ). Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer is commonly used to study mechanisms of lung and smoking-induced carcinogenesis ( Rioux & Castonguay, 1998 ; Zheng & Takano, 2011 ).…”

Cyclooxygenase‐2 in gastrointestinal malignancies

“…A natural compound, Rhizoma paridis saponins (RPS), can inhibit the growth of ESCC in both in vitro and in vivo tumor models. 14 RPS considerably suppressed tumor development in an in vivo esophageal cancer model. 14 It also decreased N-nitrosomethylbenzylaminemediated COX-2 overexpression and cyclin D1expression levels in esophageal tissues (Fig.…”

“…2). 14 RPS promoted apoptosis and cell-cycle arrest and inhibited COX-2 signaling. These results suggest that RPS may be a novel target for antitumor treatments.…”

Altering Sterol Composition Implied That Cholesterol Is Not Physiologically Associated With Diosgenin Biosynthesis in Trigonella foenum-graecum

“…For example, many in vitro experiments showed evidence that diosgenin suppressed the proliferation of a variety of cancer cells through modulating multiple signaling pathways (Sethi et al, 2018). In addition, in an intact animal mode, diosgenin was shown to inhibit the growth of rat colon tumor (Raju et al, 2004), human breast cancer (Srinivasan et al, 2009), and lung adenocarcinoma tumors (Yan et al, 2009). Those studies raise the prospect of developing diosgenin as a natural product-based antitumor drug.…”