Abstract | AIMS: 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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Authors | Min Sun Choi, Ha Jin Jeong, Tae-Hoon Kang, Heung-Mook Shin, Seung Tack Oh, Yura Choi, Songhee Jeon |
Journal | Life sciences
(Life Sci)
Vol. 141
Pg. 81-9
(Nov 15 2015)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 26382595
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Integrin beta3
- Lignans
- dihydroguaiaretic acid
- Guaiacol
- ErbB Receptors
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Down-Regulation
(drug effects)
- Enzyme Activation
(drug effects)
- ErbB Receptors
(biosynthesis, genetics)
- Female
- Genes, src
(drug effects)
- Guaiacol
(analogs & derivatives, pharmacology)
- Humans
- Integrin beta3
(biosynthesis, genetics)
- Lignans
(pharmacology)
- MCF-7 Cells
- Mammary Neoplasms, Experimental
(drug therapy)
- Mice
- p38 Mitogen-Activated Protein Kinases
(drug effects)
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