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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell

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Morais, Katia L. P. [1, 2] ; Fernandes Pacheco, Mario Thiego [2] ; Berra, Carolina Maria [3] ; Bosch, Rosemary V. [2] ; Sciani, Juliana Mozer [2] ; Chammas, Roger [4] ; Saito, Renata de Freitas [4] ; Iqbal, Asif [2] ; Chudzinski-Tavassi, Ana Marisa [1, 2]
Total Authors: 9
[1] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil
[2] Butantan Inst, Biochem & Biophys Lab, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
[4] Univ Sao Paulo, Sch Med, Expt Oncol Med Invest Lab, LIM 24, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Molecular and Cellular Biochemistry; v. 415, n. 1-2, p. 119-131, APR 2016.
Web of Science Citations: 7

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. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/05969-4 - Investigating the role of dynein in the mechanism of antitumor action of Amblyomin-X in melanoma cells and pancreatic adenocarcinoma
Grantee:Mario Thiego Fernandes Pacheco
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 98/14307-9 - Center for Applied Toxinology
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
Grantee:Kátia Luciano Pereira Morais
Support Opportunities: Scholarships in Brazil - Doctorate