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

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.

Theoretical Study of Cyclohexane -1,2-Diamine-Oxalate- Platinum Metal Complex and Comparing with Experimental Data: DFT Calculations

“…to that, we showed a strong agreement with experimental data ref. [14] , where listed in Table 2. Consequently, the present work is a suitable method a large separation was obtained between the valence and conduction bands.…”

“…In our data, one can see LUMO energy (-1.1150658eV) greater than the HOMO energies (-5.852871), these results are similar to the result ref. [14] . The energy gap is a very important parameter as a symbol of the complexes biological reactivity, as can be seen in the table 2.…”

“…This outcome is in strong alignment with that of ref. [14] , which corresponds to the high energy needed for oxaliplatinum to donate or accept an electron.…”

Reversal effect of adenovirus-mediated human interleukin 24 transfection on the cisplatin resistance of A549/DDP lung cancer cells

“…hIL-24 may exert a reversal effect on drug resistance in A549/DDP cells. P-gp pumps drugs out of cancer cells, and decreases the effect of chemotherapeutic drugs, thereby rendering cells drug-resistant ( 6 , 7 ). To further investigate whether the effect of hIL-24 was associated with P-gp, A549/DDP cells were treated with Ad-hIL-24, DDP, or Ad-hIL-24 plus DDP, and P-gp expression was detected by western-blotting.…”

“…At present, for patients with late-stage lung cancer, the main treatment strategy is chemotherapy or chemotherapy combined with radiotherapy ( 4 , 5 ). Chemotherapy can kill tumor cells, but it can also exert strong side effects on normal cells ( 6 ). Furthermore, after multiple cycles of chemotherapy, tumor cells can develop resistance to chemotherapeutic drugs.…”