title: 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.affiliation: NCI of Naples Pascale Foundation, Molecular Biology and Viral Oncogenesis, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Borrelli
authors.forename: Antonietta
authors.initials: A
authors.lastname: Schiattarella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.forename: Roberto
authors.initials: R
authors.lastname: Mancini
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.forename: Viviana
authors.initials: V
authors.lastname: De Luca
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carginale
authors.forename: Marina
authors.initials: M
authors.lastname: Sanseverino
authors.forename: Anna Lucia
authors.initials: AL
authors.lastname: Tornesello
authors.forename: Enrico
authors.initials: E
authors.lastname: Gori
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pica
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Santi
authors.forename: Filomena
authors.initials: F
authors.lastname: Basile
authors.forename: Francesca
authors.initials: F
authors.lastname: Iacobellis
authors.forename: Nicola
authors.initials: N
authors.lastname: Colacurci
authors.forename: Luigi
authors.initials: L
authors.lastname: Cobellis
authors.forename: Aldo
authors.initials: A
authors.lastname: Mancini
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D004337:Drug Carriers / Q000737:chemistry; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D004337:Drug Carriers; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2