Targeted delivery of doxorubicin to mitochondria
| Autor: | David V. Tulumello, Shana O. Kelley, Graham R. Chamberlain |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell
Antineoplastic Agents Biology Mitochondrion Biochemistry Drug Delivery Systems Organelle medicine Humans Doxorubicin Molecular Structure Topoisomerase Biological Transport General Medicine Mitochondria Enzyme Activation medicine.anatomical_structure DNA Topoisomerases Type II Cancer cell Nucleic acid biology.protein Molecular Medicine Efflux Peptides medicine.drug HeLa Cells |
| Zdroj: | ACS chemical biology. 8(7) |
| ISSN: | 1554-8937 |
| Popis: | Several families of highly effective anticancer drugs are selectively toxic to cancer cells because they disrupt nucleic acid synthesis in the nucleus. Much less is known, however, about whether interfering with nucleic acid synthesis in the mitochondria would have significant cellular effects. In this study, we explore this with a mitochondrially targeted form of the anticancer drug doxorubicin, which inhibits DNA topoisomerase II, an enzyme that is both in mitochondria and nuclei of human cells. When doxorubicin is attached to a peptide that targets mitochondria, it exhibits significant toxicity. However, when challenged with a cell line that overexpresses a common efflux pump, it does not exhibit the reduced activity of the nuclear-localized parent drug and resists being removed from the cell. These results indicate that targeting drugs to the mitochondria provides a means to limit drug efflux and provide evidence that a mitochondrially targeted DNA topoisomerase poison is active within the organelle. |
| Databáze: | OpenAIRE |
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