Title |
Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell
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Published in |
Molecular and Cellular Biochemistry, March 2016
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DOI | 10.1007/s11010-016-2683-4 |
Pubmed ID | |
Authors |
Katia L. P. Morais, Mario Thiego Fernandes Pacheco, Carolina Maria Berra, Rosemary V. Bosch, Juliana Mozer Sciani, Roger Chammas, Renata de Freitas Saito, Asif Iqbal, Ana Marisa Chudzinski-Tavassi |
Abstract |
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 [Ca(2+)] 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. |
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Demographic breakdown
Readers by professional status | Count | As % |
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Professor | 2 | 6% |
Other | 2 | 6% |
Unknown | 10 | 30% |
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Other | 4 | 12% |
Unknown | 12 | 36% |