Blockade of the Lysophosphatidylserine Lipase ABHD12 Potentiates Ferroptosis in Cancer Cells.
2020
Ferroptosis is a type of cell death
caused by the pathogenic accumulation
of lipid hydroperoxides. Pharmacological mechanisms to induce ferroptosis
may provide a way to kill cancer cells that are resistant to other
forms of cell death like apoptosis. Nonetheless, the proteins that
regulate ferroptotic sensitivity in cancer cells remain incompletely
understood. Here, we screened a panel of inhibitors of serine hydrolasesan
enzyme class important for regulating lipid metabolismfor
potentiation of ferroptosis in HT1080 fibrosarcoma cells. We found
that DO264, a selective inhibitor of the lyso- and ox-phosphatidylserine
(PS) lipase ABHD12, enhances ferroptotic death caused by RSL3, an
inhibitor of the lipid peroxidase GPX4. RSL3-induced ferroptosis was
also potentiated by genetic disruption of ABHD12. Metabolomic experiments
revealed that, in addition to elevated lyso-PS, ABHD12-inactivated
cells show higher quantities of arachidonate (C20:4)-containing PS
and 2-arachidonoyl glycerol, pointing to potential oxidation-sensitive
lipid mediators of ferroptosis regulated by ABHD12.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
38
References
12
Citations
NaN
KQI