Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell
Morais, Katia Luciano Pereira [UNIFESP]
Fernandes Pacheco, Mario Thiego
Berra, Carolina Maria
Bosch, Rosemary V.
Sciani, Juliana Mozer
Chammas, Roger [UNIFESP]
Saito, Renata de Freitas
Chudzinski-Tavassi, Ana Marisa [UNIFESP]
É parte deMolecular And Cellular Biochemistry
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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.
CitaçãoMolecular And Cellular Biochemistry. Dordrecht, v. 415, p. 119-131, 2016.
Endoplasmic reticulum stress
Antitumor drug candidate
Agência(s) de FomentoSao 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
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