Abstract
Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total protein (TP) and albumin (ALB) indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.
Highlights
Rabdosia rubescens is a herb renowned in ancient Chinese folk medicine for its antibacterial, anti-inflammatory, and antitumor properties [1,2]
These results indicated that JD and Oridonin both have significant inhibitory effects on human esophageal cell lines in a time- and dose- dependent manner, but JD exhibits more sensitivity to human esophageal cells compared with Oridonin
Normal cell lines (GES-1 and HL7702) were treated with JD, and these results showed that treatment with low concentrations of JD resulted in almost no disruption in cells; with increased concentrations and extended treatment times, cell viability was inhibited
Summary
Rabdosia rubescens is a herb renowned in ancient Chinese folk medicine for its antibacterial, anti-inflammatory, and antitumor properties [1,2]. Many studies have focused on investigating the chemical composition of Rabdosia rubescens. Studies have focused on defining the potential antitumor properties of the active diterpenoid components found in Rabdosia rubescens [7,8]. An active diterpenoid compound found in Rabdosia rubescens, has been widely used in the treatment of human diseases ranging from inflammation to cancer [9,10]. To improve its cell membrane permeability and chemical stability, we synthesized several derivatives of Oridonin. Of these compounds, Jesridonin (JD, Fig 1) demonstrated the predicted effect in both of these aspects. We examined the effect of Jesridonin treatment on human esophageal carcinoma cell proliferation and apoptosis and evaluated its adverse effects. We investigated the molecular mechanism underlying its antitumor activity
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