AI Article Synopsis
- Meso-dihydroguaiaretic acid (MDA) demonstrates significant anti-cancer properties in breast cancer cell lines and in a mouse model, highlighting its potential as a chemotherapeutic agent.
- MDA induces apoptosis through activation of specific proteins (p38 and caspase-3) and reduces the expression of proteins involved in cell cycle progression and migration.
- The study's findings support MDA's role in suppressing tumor growth and suggest that it could be developed into a treatment for breast cancer.
Article Abstract
Aims: Meso-dihydroguaiaretic acid (MDA) is known for its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-tumor activity. However, the anti-breast cancer effect and the mechanism of MDA remain undefined.
Main Methods: In this study, we examined the anti-cancer activity and the mechanisms of action of MDA in breast cancer cell lines, 4T-1 and MCF-7 cells; and 4T-1 bearing mouse model.
Key Findings: MDA showed cytotoxic effects on 4T-1 and MCF-7 cells in a dose-dependent manner. Moreover, MDA increased the amount of Annexin V-positive apoptotic bodies, phosphorylated JNK and p38 in 4T-1 cells. MDA also down-regulated cell-cycle dependent proteins, CDK-4 and cyclin D1; and induced cleaved caspase-3 in MDA-treated 4T-1 cells. We further verified that MDA-induced apoptosis is mediated by p38 and caspase-3 activation in 4T-1 cells. Next, we studied the effect of MDA treatment on cell migration and found that MDA significantly reduced cell migration. Moreover, MDA reduced EGFR and intergrin β3 expression, and dephosphorylated Src in a dose-dependent manner in 4T-1 cells. Furthermore, we observed in vivo effect of MDA in 4T-1 cell inoculated mice. MDA (20mg/kg/day) significantly suppressed mammary tumor volume and activated caspase-3 in tumor tissues.
Significance: These results suggest novel targets of MDA in breast cancer in vitro and in vivo, making it a potential candidate as a chemotherapeutic drug.
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| http://dx.doi.org/10.1016/j.lfs.2015.09.003 | DOI Listing |
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