Potential therapeutic role of hispidulin in gastric cancer through induction of apoptosis via NAG-1 signaling
Journal
Evidence-based Complementary and Alternative Medicine
Journal Volume
2013
Pages
518301
Date Issued
2013
Author(s)
Abstract
Gastric cancer is one of the most common malignant cancers due to poor prognoses and high mortality rates worldwide. However, an effective chemotherapeutic drug without side effects remains lacking. Saussurea involucrata (SI) Kar. et Kir., also known as snow lotus, grows in mountainous rocky habitats at 2600 m elevation in the Tian Shan and A'er Tai regions of China. The ethyl acetate extract of SI had been shown to inhibit proliferation and induce apoptosis in various tumor cells. In this study, we demonstrated that Hispidulin, active ingredients in SI, inhibits the growth of AGS gastric cancer cells. After Hispidulin treatment, NAG-1 remained highly expressed, whereas COX-2 expression was downregulated. Flow cytometric analysis indicated that Hispidulin induces G1/S phase arrest and apoptosis in time- and concentration-dependent manners. G1/S arrest correlated with upregulated p21/WAF1 and p16 and downregulated cyclin D1 and cyclin E, independent of p53 pathway. In addition, Hispidulin can elevate Egr-1 expression and ERK1/2 activity, whereas ERK1/2 inhibitor markedly attenuated NAG-1 mediated apoptosis. Taken together, Hispidulin can efficiently activate ERK1/2 signaling followed by NAG-1 constitutive expression and trigger cell cycle arrest as well as apoptosis in cancer cell. It can be a potential compound for combination therapy of gastric cancer in the future. ? 2013 Chao Yuan Yu et al.
SDGs
Other Subjects
acetic acid ethyl ester; acetylsalicylic acid; caspase 3; celecoxib; cyclin D1; cyclin E; cyclooxygenase 2; growth differentiation factor 15; hispidulin; mitogen activated protein kinase 3; nonsteroidal antiinflammatory drug activated gene 1; plant extract; protein p53; rutoside; Saussurea involucrata extract; transcription factor Egr 1; transcription factor RelA; unclassified drug; apoptosis; article; cancer cell culture; cancer growth; cell viability; concentration response; controlled study; cytotoxicity; down regulation; flow cytometry; G1 phase cell cycle checkpoint; habitat; human; human cell; priority journal; protein expression; reversed phase high performance liquid chromatography; S phase cell cycle checkpoint; Saussurea; Saussurea involucrata; senescence; signal transduction; stomach cancer; upregulation
Type
journal article