Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells

Maria Sofia Basile, Emanuela Mazzon, Tamara Krajnovic, Dijana Draca, Eugenio Cavalli, Yousef Al-Abed, Placido Bramanti, Ferdinando Nicoletti, Sanja Mijatovic, Danijela Maksimovic-Ivanic

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.

Original languageEnglish
JournalMolecules
Volume23
Issue number10
DOIs
Publication statusPublished - Sep 26 2018

Keywords

  • Apoptosis/drug effects
  • Cell Differentiation/drug effects
  • Cell Proliferation/drug effects
  • Glioblastoma/drug therapy
  • HIV Protease Inhibitors/chemistry
  • Humans
  • Lopinavir/chemistry
  • Nitric Oxide/chemistry
  • Tumor Cells, Cultured

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