Lupeol inhibits proliferation and induces apoptosis of human pancreatic cancer PCNA-1 cells through AKT/ERK pathways

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• 作者：Yan Liu (1)
  Tingting Bi (2)
  Gang Wang (1)
  Wei Dai (1)
  Guoliang Wu (1)
  Liqiang Qian (1)
  Quangen Gao (1)
  Genhai Shen (1)
  
  1. Department of General Surgery ; Wujiang No.1 People鈥檚 Hospital ; Suzhou ; 215200 ; China
  2. Department of Geriatric Ward ; Wujiang No.1 People鈥檚 Hospital ; Suzhou ; 215200 ; China
  
• 关键词：Lupeol ; Pancreatic cancer ; Apoptosis ; Cell cycle ; AKT ; ERK
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：388
• 期：3
• 页码：295-304
• 全文大小：4,956 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Neurosciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1912

文摘

Lupeol, a dietary triterpene, present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including anti-cancer activities both in vitro and in vivo. However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anti-cancer activity and the underlying mechanisms of lupeol on human pancreatic cancer proliferating cell nuclear antigen 1 (PCNA-1) cells in vitro and in vivo. Lupeol significantly inhibited the proliferation of the cells in dose- and time-dependent manners and induced apoptosis as well as cell cycle arrest in G0/G1 phase by upregulating P21 and P27 and downregulating cyclin D1. The expression of apoptosis-related proteins in cells was evaluated by western blot analysis, and we found that lupeol induced cell apoptosis by decreasing the levels of p-AKT and p-ERK. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of lupeol in PCNA-1 cells, demonstrating the important role of AKT in this process. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of p-AKT and p-ERK in tumor tissues following lupeol treatment, consistent with the in vitro results. Therefore, these findings indicate that lupeol can inhibit cell proliferation and induce apoptosis as well as cell cycle arrest of PCNA-1 cells and might offer a therapeutic potential advantage for human pancreatic cancer chemoprevention or chemotherapy.