Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell
| Autor: | Katia L.P. Morais, Carolina Maria Berra, Juliana Mozer Sciani, Mario Thiego Fernandes Pacheco, Roger Chammas, Renata de Freitas Saito, Asif Iqbal, Rosemary Viola Bosch, Ana Marisa Chudzinski-Tavassi |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Antitumor drug candidate Mitochondrion Article Kunitz-type inhibitor Arthropod Proteins 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor Cell Line Tumor hemic and lymphatic diseases medicine Humans Cytotoxic T cell Proteasome inhibitor Salivary Proteins and Peptides Endoplasmic Reticulum Chaperone BiP Melanoma Molecular Biology Caspase biology Amblyomin-X Cell Biology General Medicine Endoplasmic Reticulum Stress medicine.disease Recombinant Proteins Mitochondria Enzyme Activation Pancreatic Neoplasms 030104 developmental biology Proteasome Caspases 030220 oncology & carcinogenesis Immunology Unfolded protein response Cancer research biology.protein Endoplasmic reticulum stress medicine.drug |
| Zdroj: | Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP Molecular and Cellular Biochemistry |
| Popis: | Sao Paulo Research Foundation (FAPESP) National Council of Technological and Scientific Development (CNPq, INCTTox) Coordination of Improvement of Higher Education Personnel (CAPES) Uniao Quimica Farmaceutica Nacional During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca2+] (i) was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X. Butantan Inst, Biochem & Biophys Lab, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, Brazil Univ Sao Paulo, Sch Med, Expt Oncol Med Invest Lab, LIM 24, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil FAPESP: 2010/52669-3 FAPESP: 2010/07958-7 FAPESP: 2011/05969-4 FAPESP: CAT/CEPID 1998/14307-9 FAPESP: CETICs 2013/07467-1 Web of Science |
| Databáze: | OpenAIRE |
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