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

被引:107
作者
Li, Chenghai [1 ,2 ]
Yang, Zhengfeng [1 ,2 ]
Zhai, Chunyan [1 ,2 ]
Qiu, Wenwei [3 ]
Li, Dali [1 ,2 ]
Yi, Zhengfang [1 ,2 ]
Wang, Lei [1 ,2 ]
Tang, Jie [3 ]
Qian, Min [1 ,2 ]
Luo, Jian [1 ,2 ]
Liu, Mingyao [1 ,2 ,4 ]
机构
[1] E China Normal Univ, Inst Biomed Sci, Shanghai 200241, Peoples R China
[2] E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China
[3] E China Normal Univ, Dept Chem, Inst Med Chem, Shanghai 200241, Peoples R China
[4] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA
来源
MOLECULAR CANCER | 2010年 / 9卷
基金
中国国家自然科学基金;
关键词
PANCREATIC DUCTAL ADENOCARCINOMA; REGULATED GENE-PRODUCTS; CANCER CELLS; TNF-ALPHA; GROWTH; APOPTOSIS; PROLIFERATION; ANGIOGENESIS; EXPRESSION; TRITERPENE;
D O I
10.1186/1476-4598-9-73
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Tumor necrosis factor alpha (TNF alpha) has been used to treat certain tumors in clinic trials. However, the curative effect of TNF alpha has been undermined by the induced-NF-kappa B activation in many types of tumor. Maslinic acid (MA), a pharmacological safe natural product, has been known for its important effects as antioxidant, anti-inflammatory, and anti-viral activities. The aim of this study was to determine whether MA potentiates the anti-tumor activity of TNFa though the regulation of NF-kappa B activation. Results: In this study, we demonstrate that MA significantly enhanced TNF alpha-induced inhibition of pancreatic cancer cell proliferation, invasion, and potentiated TNF alpha-induced cell apoptosis by suppressing TNF alpha-induced NF-kappa B activation in a dose-and time-dependent manner. Addition of MA inhibited TNF alpha-induced I kappa B alpha degradation, p65 phosphorylation, and nuclear translocation. Furthermore, MA decreased the expression levels of NF-kappa B-Bregulated 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-kappa B-regulated anti-apoptotic gene expression, such as Survivin and Bcl-xl. Conclusions: Our data demonstrate that MA can potentiate the anti-tumor activities of TNF alpha and inhibit pancreatic tumor growth and invasion by activating caspase-dependent apoptotic pathway and by suppressing NF-kappa B activation and its downstream gene expression. Therefore, MA together with TNF alpha could be new promising agents in the treatment of pancreatic cancer.
引用
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页数:13
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