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A novel synthetic Asiatic acid derivative induces apoptosis and inhibits proliferation and mobility of gastric cancer cells by suppressing STAT3 signaling pathway

Authors Wang G, Jing Y, Cao LS, Gong CC, Gong ZN, Cao XR

Received 5 September 2016

Accepted for publication 8 November 2016

Published 20 December 2016 Volume 2017:10 Pages 55—66

DOI https://doi.org/10.2147/OTT.S121619

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Gang Wang,1 Yue Jing,2 Lingsen Cao,3 Changchang Gong,1 Zhunan Gong,1,3 Xiangrong Cao3

1Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, 3Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, People’s Republic of China

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.

Keywords: gastric cancer, signal transducer and activator of transcription 3, Asiatic acid derivative, cell cycle, apoptosis, invasion

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