Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes
| Autor: | Ji-Feng Shi, Weiyu Zhao, Wan-Liang Lu, Li-Min Mu, Chengxiang Zhang, Xiu-Ying Li, Nan Li, Yan Yan, Meng-Ge Sun, Xu Ma, Jia Zhou, Rui-Jun Ju |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Diagnostic Imaging
Abcg2 Berberine Biophysics Mice Nude Bioengineering ATP-binding cassette transporter Breast Neoplasms Mitochondrion Pharmacology Biomaterials chemistry.chemical_compound Mice Breast cancer Cancer stem cell medicine Animals Humans biology Cell Death Multidrug resistance-associated protein 2 Cytochromes c Membrane Proteins medicine.disease Multidrug Resistance-Associated Protein 2 Mitochondria Tumor Burden Phenotype Treatment Outcome Mitochondrial permeability transition pore chemistry Mechanics of Materials Drug Resistance Neoplasm Liposomes Ceramics and Composites biology.protein MCF-7 Cells Neoplastic Stem Cells ATP-Binding Cassette Transporters Female Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Biomaterials. 34(18) |
| ISSN: | 1878-5905 |
| Popis: | The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c, and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs. |
| Databáze: | OpenAIRE |
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