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

Abstract

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.

• Authors: Yan Liu, Tingting Bi, Gang Wang, Wei Dai, Guoliang Wu, Liqiang Qian, Quangen Gao, Genhai Shen
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 388 Issue 3 Pg. 295-304 (Mar 2015) ISSN: 1432-1912 [Electronic] Germany
• PMID: 25418891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Antineoplastic Agents
• Pentacyclic Triterpenes
• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins c-akt
• lupeol

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• MAP Kinase Signaling System (drug effects)
• Male
• Mice, Inbred BALB C
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Pentacyclic Triterpenes (pharmacology, therapeutic use)
• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins c-akt (metabolism)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays