Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells |
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| Institution: | 1. Laboratory of Tumor Immunology, Department of Immunology, Institute of Biomedical Science, University of São Paulo, avenue Prof. Lineu-Prestes, 1730 São Paulo – SP, Brazil;2. Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, São Paulo – SP, Brazil;3. Cell and Molecular Therapy Center NUCEL-NETCEM, University of São Paulo, São Paulo – SP, Brazil;1. Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Ave., Novosibirsk, Russia;2. Engelhardt Institute of Molecular Biology RAS, Vavilov Str. 32, 119991 Moscow, Russia;2. Department of Medicine, University Hospitals Case Medical Center, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH;3. Advanced Molecular Imaging, Philips Healthcare North America, Cleveland, OH;1. Department of Surgery, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA;2. Division of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA;3. Department of Surgery, Knight Cancer Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, L619, Portland, OR 97239, USA;1. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;2. Department of Pharmacology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil;3. Alchemy, Innovation, Research & Development, Department of Oncology, CIETEC/IPEN, University of Sao Paulo, Sao Paulo, Brazil;4. Medical Science, University of Sao Paulo Medical School, Sao Paulo, Brazil;5. Instituto Tecnológico da Aeronáutica, Sao Jose dos Campos, Sao Paulo, Brazil;1. A. E. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of the Russian Academy of Sciences, 420088 Kazan, Russian Federation;2. Kazan National Research Technological University, 420015 Kazan, Russian Federation;3. Korkyt Ata Kyzylorda University, 120014 Kyzylorda, Republic of Kazakhstan |
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| 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. |
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| Keywords: | Furoxan Lung cancer Apoptosis BFD-22 Sorafenib Anti-proliferative |
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