Abstract
A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER(+) cells for diagnostic purposes and clinical or immune therapy.
MeSH terms
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Amino Acid Sequence
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Cisplatin / chemistry
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Cisplatin / metabolism
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Cisplatin / pharmacology
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Drug Carriers / chemistry*
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Drug Carriers / metabolism
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Drug Carriers / pharmacology
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Drug Screening Assays, Antitumor
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Endoplasmic Reticulum / metabolism
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Fluorescein / chemistry
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Fluorescein / metabolism
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Fluorescent Dyes / chemistry
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Fluorescent Dyes / metabolism
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Humans
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Inhibitory Concentration 50
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Peptide Fragments / chemistry*
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Protein Sorting Signals
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Receptors, Estrogen / metabolism
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Recombinant Proteins / chemistry
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Superoxide Dismutase / chemistry
Substances
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Antineoplastic Agents
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Drug Carriers
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Fluorescent Dyes
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Peptide Fragments
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Protein Sorting Signals
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Receptors, Estrogen
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Recombinant Proteins
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Superoxide Dismutase
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Cisplatin
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Fluorescein