Maslinic acid potentiates the anti-tumor activity of tumor necrosis factor α by inhibiting NF-κB signaling pathway

Molecular Cancer

Research

Wenwei Qiu¹  Jie Tang¹  Zhengfang Yi²  Jian Luo²  Chunyan Zhai²  Lei Wang²  Min Qian²  Chenghai Li²  Dali Li²  Zhengfeng Yang²  Mingyao Liu³ 

[1] Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, 200241, Shanghai, China;The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China;The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 200241, Shanghai, China;Institute of Biosciences and Technology, Texas A&M Health Science Center, 77030, Houston, Texas, USA;

关键词: Pancreatic Cancer;    Pancreatic Cancer Cell;    Pancreatic Cancer Cell Line;    Transwell Invasion Assay;    Maslinic Acid;   

DOI  :  10.1186/1476-4598-9-73

 received in 2009-10-09, accepted in 2010-04-06,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTumor necrosis factor alpha (TNFα) has been used to treat certain tumors in clinic trials. However, the curative effect of TNFα has been undermined by the induced-NF-κB activation in many types of tumor. Maslinic acid (MA), a pharmacological safe natural product, has been known for its important effects as anti-oxidant, anti-inflammatory, and anti-viral activities. The aim of this study was to determine whether MA potentiates the anti-tumor activity of TNFα though the regulation of NF-κB activation.ResultsIn this study, we demonstrate that MA significantly enhanced TNFα-induced inhibition of pancreatic cancer cell proliferation, invasion, and potentiated TNFα-induced cell apoptosis by suppressing TNFα-induced NF-κB activation in a dose- and time-dependent manner. Addition of MA inhibited TNFα-induced IκBα degradation, p65 phosphorylation, and nuclear translocation. Furthermore, MA decreased the expression levels of NF-κB-regulated genes, including genes involved in tumor cell proliferation (Cyclin D1, COX-2 and c-Myc), apoptosis (Survivin, Bcl-2, Bcl-xl, XIAP, IAP-1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). In athymic nu/nu mouse model, we further demonstrated that MA significantly suppressed pancreatic tumor growth, induced tumor apoptosis, and inhibited NF-κB-regulated anti-apoptotic gene expression, such as Survivin and Bcl-xl.ConclusionsOur data demonstrate that MA can potentiate the anti-tumor activities of TNFα and inhibit pancreatic tumor growth and invasion by activating caspase-dependent apoptotic pathway and by suppressing NF-κB activation and its downstream gene expression. Therefore, MA together with TNFα could be new promising agents in the treatment of pancreatic cancer.

【 授权许可】

Unknown   
© Li et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.