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

Author(s)

Teixeira, Sarah Fernandes ^[1] ; de Azevedo, Ricardo Alexandre ^[1] ; Clavijo Salomon, Maria Alejandra ^[1] ; Jorge, Salomao Doria ^[1] ; Levy, Debora ^[2] ; Bydlowski, Sergio Paulo ^[2] ; Rodrigues, Cecilia Pessoa ^[1] ; Pizzo, Celia Regina ^[1] ; Marzagao Barbuto, Jose Alexandre ^{[1, 3]} ; Ferreira, Adilson Kleber ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, BR-1730 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Genet & Mol Hematol LIM31, BR-1730 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL NETCEM, BR-1730 Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 68, n. 8, p. 1015-1022, OCT 2014.
• Web of Science Citations: 4

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. (C) 2014 Elsevier Masson SAS. All rights reserved. (AU)

• 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: 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