1. A new hexapeptide from the leader peptide of rMnSOD enters cells through the oestrogen receptor to deliver therapeutic molecules.
- Author
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Borrelli A, Schiattarella A, Mancini R, Pica A, Pollio ML, Ruggiero MG, Bonelli P, De Luca V, Tuccillo FM, Capasso C, Gori E, Sanseverino M, Carpentieri A, Birolo L, Pucci P, Rommelaere J, and Mancini A
- Subjects
- Amino Acid Sequence, Antineoplastic Agents chemistry, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Survival drug effects, Cisplatin chemistry, Cisplatin metabolism, Cisplatin pharmacology, Drug Carriers metabolism, Drug Carriers pharmacology, Drug Screening Assays, Antitumor, Endoplasmic Reticulum metabolism, Fluorescein chemistry, Fluorescein metabolism, Fluorescent Dyes chemistry, Fluorescent Dyes metabolism, Humans, Inhibitory Concentration 50, Peptide Fragments metabolism, Peptide Fragments pharmacology, Protein Sorting Signals, Receptors, Estrogen metabolism, Recombinant Proteins chemistry, Superoxide Dismutase chemistry, Drug Carriers chemistry, Peptide Fragments chemistry
- 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.
- Published
- 2016
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