A molecular carrier to transport and deliver cisplatin into endometrial cancer cells.

Abstract

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 μM cisplatin on its own was minimal, while in the presence of 0.5 μM 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.

• Authors: Antonella Borrelli, Antonietta Schiattarella, Alessandra Musella, Roberto Mancini, Clemente Capasso, Viviana De Luca, Vincenzo Carginale, Marina Sanseverino, Anna Lucia Tornesello, Enrico Gori, Alessandra Pica, Annalisa Di Santi, Filomena Basile, Francesca Iacobellis, Nicola Colacurci, Luigi Cobellis, Aldo Mancini
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 80 Issue 1 Pg. 9-16 (Jul 2012) ISSN: 1747-0285 [Electronic] England
• PMID: 22260094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Recombinant Proteins
• Superoxide Dismutase
• superoxide dismutase 2
• Cisplatin

Topics

• Antineoplastic Agents (therapeutic use, toxicity)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (therapeutic use, toxicity)
• Drug Carriers (chemistry)
• Endometrial Neoplasms (drug therapy, pathology)
• Female
• Humans
• Immunohistochemistry
• Recombinant Proteins (genetics, metabolism)
• Spectrophotometry, Atomic
• Superoxide Dismutase (genetics, metabolism)