title: A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway.
abstract: Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative,N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Lingsen
authors.initials: L
authors.lastname: Cao
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University.
authors.forename: Changchang
authors.initials: C
authors.lastname: Gong
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Cao
keywords: Asiatic acid derivative; apoptosis; cell cycle; gastric cancer; invasion; signal transducer and activator of transcription 3