[Pt(O,O′-acac)(γ-acac)(DMS)] versus cisplatin: apoptotic effects in B50 neuroblastoma cells

• Published in: Histochemistry and cell biology Vol. 145; no. 5; pp. 587 - 601
• Main Authors: Grimaldi, Maddalena, Santin, Giada, Insolia, Violetta, Dal Bo, Veronica, Piccolini, Valeria Maria, Veneroni, Paola, Barni, Sergio, Verri, Manuela, De Pascali, Sandra Angelica, Fanizzi, Francesco Paolo, Bernocchi, Graziella, Bottone, Maria Grazia
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2016
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Cycle - drug effects; Cisplatin - chemistry; Cisplatin - pharmacology; Developmental Biology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Original Paper; Rats; Structure-Activity Relationship; Tumor Cells, Cultured; B50 neuroblastoma rat cells; Cytoplasmic organelles; PtAcacDMS; Cisplatin; Apoptosis
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-015-1396-1

Cisplatin is one of the most active chemotherapeutic agents used in the treatment of childhood and adult malignancies. Cisplatin induces cell death through different pathways. Despite its effectiveness, the continued clinical use of cisplatin is limited by onset of severe side effects (nephrotoxicity, ototoxicity and neurotoxicity) and drug resistance. Therefore, one of the main experimental oncology purpose is related to the search for new platinum-based drugs to create different types of adducts or more specific and effective subcellular targets. Thus, [Pt(O,O ′ -acac)(γ-acac)(DMS)], which reacts preferentially with protein thiols or thioether, was synthesized. In our research, different approaches were used to compare cisplatin and [Pt( O,O′ -acac)(γ-acac)(DMS)] effects in B50 rat neuroblastoma cells. Our results, using immunocytochemical, cytometric and morphological techniques, showed that these compounds exert a cytostatic action and activate apoptosis with different pathways. Long-term effects demonstrated that [Pt( O,O′ -acac)(γ-acac)(DMS)] exerts cytotoxic effects in neuronal B50 cell line not inducing drug resistance. Analysis was performed both to compare the ability of these platinum compounds to induce cell death and to investigate the intracellular mechanisms at the basis of their cytotoxicity.