A hybrid spatiotemporal model of PCa dynamics and insights into optimal therapeutic strategies

Burbanks, Andrew; Cerasuolo, Marianna; Ronca, Roberto; Turner, Leo

doi:10.1016/j.mbs.2022.108940

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…For combination studies with androgen deprivation therapy, TRAMP mice were treated with enzalutamide (3 mg/kg) in the drinking water from 12 week of age until 25 week of age in combination or not with sub-optimal doses of RSL3 + iron dextran (5 mg/kg/week RSL3, 10 mg/kg/week iron dextran). At week 25 mice were sacrificed and prostates processed as described in [ 20 , 43 ].…”

Section: Methodsmentioning

confidence: 99%

“…In this work we exploit an “integrated platform” represented by human and murine PCa cells and the in vivo multistage TRAMP mouse model [ 19 , 20 ] to better define the therapeutic potential of ferroptosis in naïve and androgen independent settings [ 21 ]. We show that RSL3 efficiently induces ferroptosis in human and murine PCa cells and demonstrate for the first time that iron supplementation potentiates RSL3-induced ferroptosis in PCa cells in vitro, in vivo, and in the multistage TRAMP model of PCa.…”

Section: Introductionmentioning

confidence: 99%

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Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer

et al. 2023

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Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa.

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Section: Methodsmentioning

confidence: 99%