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Aim: Cucurbitacin B (Cuc B), a natural triterpenoid with potent anti-cancer activities both in vitro and in vive, induces cancer cells cycle arrest at S or G2/M phases while the detailed mechanisms remain to be clear.This study was designed to precisely dissect mechamsms responsible for Cuc B-induced cell cycle arrest in human lung adenocarcinoma epithelial A549 cells.