GNPS - Metabolic consequences of erastin-induced ferroptosis in human ovarian cancer cells

Ovarian cancer has been difficult to cure due to acquired or intrinsic resistance Q10
and therefore, newer or more effective drugs/approaches are needed for
a successful treatment in the clinic. Erastin (ER), a ferroptosis inducer, kills
tumor cells by generating and accumulating reactive oxygen species (ROS)
within the cell, resulting in an iron-dependent oxidative damage-mediated
ferroptotic cell death. We have utilized human ovarian cancer cell lines, OVCAR-
8 and its adriamycin-selected, multi-drug resistance protein (MDR1)-expressing
NCI/ADR-RES, both equally sensitive to ER, to identify metabolic biomarkers
of ferroptosis. Our studies showed that ER treatment rapidly depleted cellular
glutathione and cysteine and enhanced formation of ophthalamate (OPH) in
both cells. Opthalalmate has been proposed to be a biomarker of oxidative
stress in cells. Our study also found significant decreases in cellular taurine, a
natural antioxidant in cells. Additionally, we found that ER treatment decreased
cellular levels of NAD+/NADP+, carnitines and glutamine/glutamate in both
cells, suggesting significant oxidative stress, decrease in energy production,
and cellular and mitochondrial disfunctions, leading to cell death. Our studies
identified several potential biomarkers of ER-induced ferroptosis including OPH,
taurine, NAD+, NADP+ and glutamate in ovarian cancer cells. Identifying specific
metabolic biomarkers that are predictive of whether a cancer is susceptible to
ferroptosis will help us devise more successful treatment modalities.