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

Author(s)

Teixeira, Sarah Fernandes ; de Azevedo, Ricardo Alexandre ; Silva, Arthur Carvalho ; Braga, Rodolpho Campos ; Jorge, Salomao Doria ; Marzagao Barbuto, Jose Alexandre ; Andrade, Carolina Horta ; Ferreira, Adilson Kleber

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 84, p. 1019-1028, DEC 2016.
• Web of Science Citations: 1

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. (C) 2016 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 16/05351-4 - Development of new drug candidate for the treatment of non-small cell lung cancer: CHY-1 as a novel inhibitor of autophagy and prototype of a novel class of inhibitors of the enzyme CTP: phosphoethanolamine citidililtransferase
• Grantee: Adilson Kleber Ferreira
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach
• Grantee: Jose Alexandre Marzagão Barbuto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/05396-0 - RATIONAL DESING AND DEVELOPMENT OF NEW PROTOTYPES DERIVED OF ANTITUMOR PHOSPHOLIPIDS AS POTENTIAL INHIBITORS OF THE ENZIME CTP:PHOSPHOETHANOLAMINE CITIDILILTRANSFERASE AND ANTITUMOR AGENTS IN NON-SMALL CELL LUNG CANCER.
• Grantee: Adilson Kleber Ferreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/18528-7 - Development of new drug candidate for the treatment of non-small cell lung cancer: CHY-1 as a novel inhibitor of autophagy and prototype of a novel class of inhibitors of the enzyme CTP: phosphoethanolamine citidililtransferase
• Grantee: Adilson Kleber Ferreira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/07341-0 - Evaluation of antitumor effects of new antineoplastic phospholipids analogous an inhibitor of the enzyme CtP: phosphoethanolamine citidililtransferase in non-small cell lung cancer
• Grantee: Adilson Kleber Ferreira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/24455-0 - Evaluation of the activity of CHY-1, a novel miltefosine analogue, as a potential CTP: phosphoethanolamine cytidylyltransferase enzyme inhibitor, against non-small cell lung câncer
• Grantee: Sarah Fernandes Teixeira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/07273-2 - Rational design and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzyme CtP: phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer
• Grantee: Jose Alexandre Marzagão Barbuto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/14267-1 - Multi-target potentially antitumor agents for malignant melanoma: rational design, synthesis, and biological assays of novel benzofuroxan derivatives
• Grantee: Salomão Dória Jorge
• Support Opportunities: Scholarships in Brazil - Post-Doctoral