Pharmacological Vitamin C-induced high H2O2 generation mediates apoptotic cell death by caspase 3/7 activation in breast cancer tumor spheroids
https://translational-medicine.biomedce ... 24-06016-7
Results
We showed that Vit-C induced dose-dependent cell death in both types of tumor spheroids, primarily driven by elevated H2O2 production and a concomitant oxidative stress imbalance induced by the GSH depletion. The high levels of H2O2 generated by Vit-C triggered the apoptosis of spheroids. In MCF-7 spheroids, Vit-C-induced H2O2 production was higher, with a more pronounced decrease in the GSH/GSSG ratio, indicating greater susceptibility to oxidative stress-induced cell death. However, MDA-MB-231 spheroids exhibited a more severe cytotoxic response.
Conclusions
This study reveals that Vit-C induces oxidative stress-mediated cell death in both non-aggressive and aggressive BC spheroids. Unlike traditional in vitro studies, this work provides novel insights into the response of two BC tumor subtypes to Vit-C, demonstrating its potential as a targeted common therapy for BC.
...we selected five pharmacological concentrations of high-dose Vit-C (1, 5, 10, 15, and 20 mM). After 72 h, Vit-C largely disrupted the morphology and induced cytotoxicity in both spheroids in a dose-dependent manner (Fig. 2A).
Notably, compared with other doses, the 20 mM produced the severest morphological disintegration in both cancer spheroids. Although the effects were most pronounced after 72 h, the outer cellular debris formation and the residual spheroidal body generation started from 24 h after Vit-C administration (Fig. 2A).