Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells.

Abstract

Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.

• Authors: Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Maria Alejandra Clavijo Salomon, Salomão Dória Jorge, Débora Levy, Sérgio Paulo Bydlowski, Cecília Pessoa Rodrigues, Célia Regina Pizzo, José Alexandre Marzagão Barbuto, Adilson Kleber Ferreira
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 68 Issue 8 Pg. 1015-22 (Oct 2014) ISSN: 1950-6007 [Electronic] France
• PMID: 25312819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzoxazoles
• Phenylurea Compounds
• Niacinamide
• benzofuroxan
• Sorafenib

Topics

• Antineoplastic Agents (administration & dosage)
• Benzoxazoles (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Drug Therapy, Combination
• Humans
• Lung Neoplasms (drug therapy)
• Niacinamide (administration & dosage, analogs & derivatives)
• Phenylurea Compounds (administration & dosage)
• Sorafenib