Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells.

Abstract

The antitumor activity of oleanolic (OA) has attracted attention due to its marked antitumor effects and pharmacological safety. In the present study, the effects of the combination of OA and 5-fluorouracil (5-FU) on Panc-28 human pancreatic cells were studied. The results showed that combined use of OA and 5-FU synergistically potentiated cell death effects on Panc-28 cells, and the pro-apoptotic effects were also increased. Further study revealed that the combined treatment could enhance mitochondrial depolarization, lysosomal membrane permeabilization (LMP) and leakage of cathepin D, while the release of cytochrome C did not display significant changes. The expression of apoptosis related proteins was also affected in cells treated with the combination of OA and 5-FU, including activation of caspases-3 and the expression of Bcl-2/Bax, survivin and NF-κB. Our results provide evidence that combination of OA and 5-FU may serve as a novel strategy for the treatment of pancreatic cancer.

• Authors: Jianteng Wei, Haizhou Liu, Ming Liu, Ning Wu, Jin Zhao, Lin Xiao, Lijun Han, Edward Chu, Xiukun Lin
• Journal: Oncology reports (Oncol Rep) Vol. 28 Issue 4 Pg. 1339-45 (Oct 2012) ISSN: 1791-2431 [Electronic] Greece
• PMID: 22825128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Survivin
• bcl-2-Associated X Protein
• Oleanolic Acid
• Cytochromes c
• Caspase 3
• CTSD protein, human
• Cathepsin D
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cathepsin D (metabolism)
• Cell Proliferation (drug effects)
• Cytochromes c (metabolism)
• Drug Screening Assays, Antitumor
• Fluorouracil (administration & dosage, pharmacology)
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Intracellular Membranes (drug effects)
• Lysosomes (drug effects)
• NF-kappa B (metabolism)
• Oleanolic Acid (administration & dosage, pharmacology)
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Permeability
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Survivin
• Tumor Cells, Cultured (drug effects)
• bcl-2-Associated X Protein (metabolism)