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

Teixeira, Sarah Fernandes; de Azevedo, Ricardo Alexandre; Silva, Arthur Carvalho; Braga, Rodolpho Campos; Jorge, Salomão Dória; Barbuto, José Alexandre Marzagão; Andrade, Carolina Horta; Ferreira, Adilson Kleber; (2016) Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells. BIOMEDICINE & PHARMACOTHERAPY, 84. pp. 1019-1028. ISSN 0753-3322 DOI: https://doi.org/10.1016/j.biopha.2016.10.025

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.