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A Molecular Carrier to Transport and Deliver Cisplatin into Endometrial Cancer Cells
Author(s) -
Borrelli Antonella,
Schiattarella Antonietta,
Musella Alessandra,
Mancini Roberto,
Capasso Clemente,
De Luca Viviana,
Carginale Vincenzo,
Sanseverino Marina,
Tornesello Anna Lucia,
Gori Enrico,
Pica Alessandra,
Di Santi Annalisa,
Basile Filomena,
Iacobellis Francesca,
Colacurci Nicola,
Cobellis Luigi,
Mancini Aldo
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01337.x
Subject(s) - cisplatin , clonogenic assay , apoptosis , chemistry , cancer cell , cancer research , endometrial cancer , microbiology and biotechnology , cancer , biology , biochemistry , medicine , chemotherapy
The leader peptide of a recombinant manganese superoxide dismutase (rMnSOD‐Lp) acts as a molecular carrier. Clonogenic tests on normal (MRC‐5) and endometrial adenocarcinoma cells (HTB‐112) were carried out in the presence of rMnSOD‐Lp, cisplatin alone (CC) or cisplatin conjugated to the rMnSOD‐Lp (rMnSOD‐Lp‐CC). The platinum delivered into the cells was measured by atomic spectrophotometric absorbance. The treatments on tumor and normal cells were finally evaluated by LM and TM microscopy. Tumor cell death in the case of 0.5 μ m cisplatin on its own was minimal, while in the presence of 0.5 μ m rMnSOD‐Lp‐CC, no tumor cells survived. Atomic absorbance analysis showed that rMnSOD‐Lp‐CC delivered approximately four times more cisplatin into HTB‐112 cells than the amount delivered using cisplatin alone. By LM observation, the cells treated with rMnSOD‐Lp‐CC showed signs of nuclear and cytoplasmic fragmentation, that is, apoptosis induced by the treatment. The therapeutic effect of rMnSOD‐Lp‐CC on endometrial cancer cells was significant, while on the normal cells it showed only a minimal toxicity. We believe that rMnSOD‐Lp deserves to be considered as a molecular carrier to deliver cisplatin directly into tumor cells, thus transforming its antireplicative activity into a specific and selective antitumor agent.