Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells

Biomed Pharmacother. 2016 Dec;84:1019-1028. doi: 10.1016/j.biopha.2016.10.025. Epub 2016 Oct 18.

Abstract

Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose. This study presents LabMol-12, a new pyridinyl carboxamide derivative with antileishmanial and antichagasic activity, as a new hit for lung cancer treatment, which induces apoptosis dependent of caspases in NCI-H1299 lung cancer cells both in monolayer and 3D culture. Moreover, LabMol-12 allows a reduction of oxaliplatin dose when they are combined, thereby, it is a relevant strategy for reducing the side effects of oxaliplatin with the same response. Molecular modeling studies corroborated the biological findings and suggested that the combined therapy can provide a better therapeutically profile effects against NSCLC. All these findings support the fact that the combination of oxaliplatin and LabMol-12 is a promising drug combination for lung cancer.

Keywords: Apoptosis; Lung cancer; Oxaliplatin; Pyridinyl carboxamide derivative; Synergism.

MeSH terms

  • Amides / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Models, Molecular
  • Molecular Structure
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • Pyridines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Organoplatinum Compounds
  • Pyridines
  • Oxaliplatin