Ferroptosis holds great potential as a therapeutic approach
for
gastric cancer (GC), a prevalent and deadly malignant tumor associated
with high rates of incidence and mortality. Myricetin, well-known
for its multifaceted biomedical attributes, particularly its anticancer
properties, has yet to be thoroughly investigated regarding its involvement
in ferroptosis. The aim of this research was to elucidate the impact
of myricetin on ferroptosis in GC progression. The present study observed
that myricetin could trigger ferroptosis in GC cells by enhancing
malondialdehyde production and Fe2+ accumulation while
suppressing glutathione levels. Mechanistically, myricetin directly
interacted with NADPH oxidase 4 (NOX4), influencing its stability
by inhibiting its ubiquitin degradation. Moreover, myricetin regulated
the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment
significantly inhibited the growth of subcutaneous tumors in BALB/c
nude mice. It was accompanied by increased NOX4 expression in tumor
tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore,
this research underscores myricetin as a novel inducer of ferroptosis
in GC cells through its interaction with NOX4. It is a promising candidate
for GC treatment.