Evodiamine Induces Extrinsic Apoptosis Through P38 Mapk Pathway and Inhibits Autophagy in Gallbladder Cancer
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 6, Issue 3
Abstract
The gallbladder cancer is the most common malignant tumor of the biliary tract and the third most common gastrointestinal malignant tumor in the world for public health with extremely poor prognosis. The primary purpose of this study is to investigate the inhibition effects of evodiamine, a major alkaloid compound extracted from the dry unripened fruit Evodiae fructus, on the carcinoma of the gallbladder cancer, and explored the underlying molecular mechanisms responsible for these effects. Cell viability of NOZ and GBC-SD cells was assessed by CCK-8 and colony forming assays. Cell apoptosis was analyzed by Annexin V-FITC and PI double staining flow cytometry and the apoptosis-related DNA damage was detected by Immunofluorescence microscopy assays. Western blot analysis was used to analyze the expression of crucial proteins involved in apoptosis, autophagy and signaling pathways. In this study, we found evodiamine induced cell viability and colony forming inhibition, apoptosis promotion and autophagy inhibition of NOZ and GBC-SD cells in a dose-dependent manner. The activation of p38 MAPK signaling pathway was significantly associated with evodiamine-treated apoptosis of gallbladder cancer cells, and the depletion of p53 was related with decreasing autophagy. Consequently, we propose that evodiamine may serve as a potential therapeutic agent for gallbladder cancer.Gallbladder cancer is the most common malignancy of the biliary tract. It is a lethal disease for most patients with a very poor prognosis and the 5-year survival rate is less than 5%~10% [1-3]. The etiology of gallbladder carcinoma remains poorly understood, yet the epidemiological studies have showed great disparities in geography, ethnic and gender [4,5]. Due to its inconspicuous signs and vague symptom, early diagnosis is hard and thus surgical resection is the only potentially curative therapy for many patients. Nevertheless, most of these patients suffer from recurrence or failure of the operation and require more radical therapy [6]. For these patients and those with unresectable gallbladder carcinoma, chemotherapy and radiotherapy are the remaining options, however, the therapeutic effect is not satisfactory at present. Accordingly, novel therapeutic strategies and potential anticancer drugs against gallbladder cancer are urgently needed. Evodiamine (EVO, Figure 1A) is a major alkaloid compound extracted from the dry unripened fruit Evodiae fructus, which has been found to be effective in the treatment of metabolic disorders, neurological disorders, and cardiovascular disorders [7,8].
Authors and Affiliations
Jun jie Xu, Ran Yang, Fang jing Yang, Ying bin Liu
Keywords
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- EP ID EP588474
- DOI 10.26717/BJSTR.2018.06.001347
- Views 169
- Downloads 0
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