pCramoll and rCramoll lectins induce cell death in human prostate adenocarcinoma (PC-3) cells by impairment of mitochondrial homeostasis

Author(s)

Figueiroa, Evellyne de Oliveira ; Aranda-Souza, Mary Angela ; Varejao, Nathalia ; Rossato, Franco Aparecido ; Pereira Costa, Rute Alves ; Figueira, Tiago Rezende ; Nascimento da Silva, Luis Claudio ; Castilho, Roger Frigerio ; Vercesi, Anibal Eugenio ; dos Santos Correia, Maria Tereza

• Document type: Journal article
• Source: TOXICOLOGY IN VITRO; v. 43, p. 40-46, SEP 2017.
• Web of Science Citations: 1

Abstract

Lectins from Cratylia molls seed have shown potential in vivo antitumor actions, however the mechanism have not yet been addressed. Here we evaluated the antitumor effects of native (pCramoll) and recombinant (rCramoll) lectins from C. mollis against human prostate adenocarcinoma (PC-3) cells. The viability of PC-3 cells was analyzed with the MIT assay and ANNEXIN V/propidium iodide staining. The actions of pCramoll or rCramoll on mitochondrial superoxide production, free cytosolic calcium concentration and mitochondrial membrane potential were evaluated using fluorescent probes (MitoSox Red, Fura 2-AM and safranin 0, respectively). pCramoll and rCramoll reduced the viability of PC-3 cells in a dose-dependent manner. Both lectins increased the generation of mitochondrial superoxide as well as the concentration of cytosolic calcium. These changes led to a decrease in oxidative phosphorylation, which impaired the formation of ATP. The resulting cell death was not blocked by MPT (mitochondrial permeability transition) inhibitors (Debio 025 or bongkrekic acid). Thus pCramoll and rCramoll promote PC-3 cell death through calcium signaling, leading to mitochondrial collapse. This work provides more insights into the action of pCramoll and rCramoll against cancer cells. These lectins represent valuable tools for biomedical research. (AU)

• FAPESP's process: 11/51800-1 - Muscle damage induced by eccentric exercise: involvement of mitochondria and interactions with statin myotoxicity
• Grantee: Tiago Rezende Figueira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
• Grantee: Aníbal Eugênio Vercesi
• Support type: Research Projects - Thematic Grants