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AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

Authors Jing Y, Wang G, Ge Y, Xu M, Tang S, Gong Z

Received 21 October 2015

Accepted for publication 16 January 2016

Published 17 March 2016 Volume 2016:9 Pages 1605—1621

DOI https://doi.org/10.2147/OTT.S98849

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Chang Liu

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Yue Jing,1 Gang Wang,1 Ying Ge,1 Minjie Xu,1 Shuainan Tang,1 Zhunan Gong1,2

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

Abstract: Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

Keywords: Asiatic acid derivatives, gastric cancer cells, anti-tumor effect, cytotoxicity, apoptosis, cell cycle arrest, migration, invasion, mobility
 

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