| Full text | |
| Author(s): |
Bonturi, Camila Ramalho
;
Salu, Bruno Ramos
;
Bonazza, Camila Nimri
;
Sinigaglia, Rita de Cassia
;
Rodrigues, Tiago
;
Alvarez-Flores, Miryam Paola
;
Chudzinski-Tavassi, Ana Marisa
;
Oliva, Maria Luiza Vilela
Total Authors: 8
|
| Document type: | Journal article |
| Source: | Molecules; v. 27, n. 9, p. 22-pg., 2022-05-01. |
| Abstract | |
Cell adhesion and migration are crucial for cancer progression and malignancy. Drugs available for the treatment of metastatic melanoma are expensive and unfit for certain patients. Therefore, there is still a need to identify new drugs that block tumor cell development. We investigated the effects of Enterolobium contortisiliquum trypsin inhibitor (EcTI), a protease inhibitor, on cell viability, cell migration, invasion, cell adhesion, and cell death (hallmarks of cancer) in vitro using human melanoma cells (SK-MEL-28 and CHL-1). Although EcTI did not affect non-tumor cells, it significantly inhibited the proliferation, migration, invasion, and adhesion of melanoma cells. Investigation of the underlying mechanisms revealed that EcTI triggered apoptosis and nuclear shrinkage, increased PI uptake, activated effector caspases-3/7, and produced reactive oxygen species (ROS). Furthermore, EcTI disrupted the mitochondrial membrane potential, altered calcium homeostasis, and modified proteins associated with survival and apoptosis/autophagy regulation. Acridine orange staining indicated acidic vesicular organelle formation upon EcTI treatment, demonstrating a cell death display. Electronic microscopy corroborated the apoptotic pattern by allowing the visualization of apoptotic bodies, mitochondrial cristae disorganization, and autophagic vesicles. Taken together, these results provide new insights into the anti-cancer properties of the natural EcTI protein, establishing it as a promising new therapeutic drug for use in melanoma treatment. (AU) | |
| FAPESP's process: | 17/06630-7 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action |
| Grantee: | Maria Luiza Vilela Oliva |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/22243-9 - Fragments derived from the structure of protease inhibitors with selectivity for inhibition of mammalian and microorganism enzymes and its role as an anti-inflammatory, antimicrobial, antithrombotic and anti- tumor agent: mechanism of action |
| Grantee: | Camila Ramalho Bonturi |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |