Ethyl gallate suppresses proliferation and invasion in human breast cancer cells via Akt-NF-κB signaling.

Abstract

Euphorbia fischeriana Steud is a traditional Chinese Medicine that is known to possess a variety of anticarcinogenic properties. However, the bioactive constituents in Euphorbia fischeriana Steud and molecular mechanisms underlying this action in cancer treatment remain poorly understood. The present study investigated the chemotherapy activity and molecular targets of Ethyl gallate, which is identified as the major constituent extracted from the roots of Euphorbia fischeriana Steud in breast cancer cell lines in vitro. The results showed Ethyl gallate obviously decreased cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner. Highly invasive MDA-MB-231 cells were found to be highly sensitive to treatment. Furthermore, significantly decreased metastatic potential of highly metastatic MDA-MB‑231 cells by Ethyl gallate was identified via the inhibition of cell motility using invasion and migration through a polyethylene terephthalate membrane. Ethyl gallate treatment decreased the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 by the downregulation of mRNA levels using RT-PCR, enzymes that are critical to tumor invasion. Treatment with Ethyl gallate decreased phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor-κB (NF-κB) activation in MDA-MB-231 cells. These results indicate that Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells. Thus, the present study shed new light on Ethyl gallate, an important bioactive constituent of Euphorbia fischeriana Steud, in human breast cancer treatment. The findings may provide basal theories for wide therapeutic application in human breast cancer.

• Authors: Hongxia Cui, Jiaxin Yuan, Xiaohui Du, Ming Wang, Liling Yue, Jicheng Liu
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 3 Pg. 1284-90 (Mar 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25522911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plant Extracts
• RELA protein, human
• RNA, Messenger
• Transcription Factor RelA
• bcl-2-Associated X Protein
• ethyl gallate
• Gallic Acid
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Enzyme Activation (drug effects)
• Euphorbia (metabolism)
• Female
• Gallic Acid (analogs & derivatives, pharmacology)
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness (pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (biosynthesis)
• Signal Transduction (drug effects)
• Transcription Factor RelA (metabolism)
• bcl-2-Associated X Protein (metabolism)