The Analysis of the Anti-Tumor Mechanism of Ursolic Acid Using Connectively Map Approach in Breast Cancer Cells Line MCF-7

Background: Ursolic acid (UA), a primary bioactive triterpenoid, was reported as an anti-cancer agent. However, the current knowledge of UA and its potential anti-cancer mechanisms and targets in breast cancer cells are limited. In this study, we aimed to illustrate the potential mechanisms and targets of UA in breast cancer cells MCF-7.

Methods: The effect of UA on cell growth was determined in MCF-7 cells by MTT assay. The anti-tumor mechanism of UA was evaluated by microarray, CAMP, and Western blot. Moreover, the molecular docking between UA and potential receptors were predicted by iGEMDOCK software.

Results: The result of MTT assay demonstrated that UA could inhibit MCF-7 cell growth with IC₅₀ values of 20 μM. Microarray and CMAP analysis, validated by Western blot, indicated that UA significantly modulated IKK/NF-κB, RAF/ERK pathways, and down-regulated the phosphorylation level of PLK1 in MCF-7 cells.

Conclusion: Our data indicated that the anti-tumor effects of UA are due to the inhibited RAF/ERK pathway and IKK/NF-κB pathway. It could also be explained by the reduced phosphorylation of PLK1 in MCF-7 cells. This study provides a new insight for deep understanding of the new anti-cancer mechanisms of UA in MCF-7 breast cancer cells.

Keywords: PLK1; RAF/ERK; connectivity map; ursolic acid; IKK/NF-κB.