title: AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.
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.
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Xu
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China.
authors.forename: Shuainan
authors.initials: S
authors.lastname: Tang
authors.affiliation: Center for New Drug Research and Development, Nanjing Normal University, Nanjing, People's Republic of China; 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
keywords: Asiatic acid derivatives; anti-tumor effect; apoptosis; cell cycle arrest; cytotoxicity; gastric cancer cells; invasion; migration; mobility