Roberto Fernández-Acosta
@uantwerpen.be
Postdoctoral researcher
University of Antwerp
EDUCATION
2018-02-01 to 2023-01-10 | Ph.D. in Pharmaceutical Sciences, Institute of Pharmacy and Food (IFAL), University of Havana
2015-09-01 to 2017-07-17 | Master of Pharmacology, Institute of Pharmacy and Food (IFAL), University of Havana
2010-09-01 to 2015-07-03 | BSc in Radiochemistry, Higher Institute of Technologies and Applied Sciences (InSTEC), University of Havana
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Biochemistry, Genetics and Molecular Biology, Biomaterials, Pharmacology, Toxicology and Pharmaceutics
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Osmany Cuesta-Rubio, Lianet Monzote, Roberto Fernández-Acosta, Gilberto Lázaro Pardo-Andreu, and Luca Rastrelli
Elsevier BV
Roberto Fernández-Acosta, Behrouz Hassannia, Jurgen Caroen, Bartosz Wiernicki, Daniel Alvarez-Alminaque, Bruno Verstraeten, Johan Van der Eycken, Peter Vandenabeele, Tom Vanden Berghe, and Gilberto L. Pardo-Andreu
MDPI AG
Ferroptosis is an iron-dependent cell death-driven by excessive peroxidation of polyunsaturated fatty acids (PUFAs) of membranes. A growing body of evidence suggests the induction of ferroptosis as a cutting-edge strategy in cancer treatment research. Despite the essential role of mitochondria in cellular metabolism, bioenergetics, and cell death, their function in ferroptosis is still poorly understood. Recently, mitochondria were elucidated as an important component in cysteine-deprivation-induced (CDI) ferroptosis, which provides novel targets in the search for new ferroptosis-inducing compounds (FINs). Here, we identified the natural mitochondrial uncoupler nemorosone as a ferroptosis inducer in cancer cells. Interestingly, nemorosone triggers ferroptosis by a double-edged mechanism. In addition to decreasing the glutathione (GSH) levels by blocking the System xc cystine/glutamate antiporter (SLC7A11), nemorosone increases the intracellular labile Fe2+ pool via heme oxygenase-1 (HMOX1) induction. Interestingly, a structural variant of nemorosone (O-methylated nemorosone), having lost the capacity to uncouple mitochondrial respiration, does not trigger cell death anymore, suggesting that the mitochondrial bioenergetic disruption via mitochondrial uncoupling is necessary for nemorosone-induced ferroptosis. Our results open novel opportunities for cancer cell killing by mitochondrial uncoupling-induced ferroptosis.
Roberto Fernández-Acosta, Claudia Iriarte-Mesa, Daniel Alvarez-Alminaque, Behrouz Hassannia, Bartosz Wiernicki, Alicia M. Díaz-García, Peter Vandenabeele, Tom Vanden Berghe, and Gilberto L. Pardo Andreu
MDPI AG
The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP–GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP–GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP–GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.
María Ángeles Bécquer-Viart, Adonis Armentero-López, Daniel Alvarez-Almiñaque, Roberto Fernández-Acosta, Yasser Matos-Peralta, Richard F. D’Vries, Javier Marín-Prida, and Gilberto L. Pardo-Andreu
MDPI AG
The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC50 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos–Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.
Javier Marín-Prida, Gilberto L. Pardo Andreu, Camila Pederiva Rossignoli, Michael González Durruthy, Estael Ochoa Rodríguez, Yamila Verdecia Reyes, Roberto Fernández Acosta, Sergio A. Uyemura, and Luciane C. Alberici
Elsevier BV