2024 Theses Doctoral

Exploring the effects of dietary fatty acids and iron on modulating sensitivity of lymphomas to ferroptosis

Ahmed, Eman Riaz

Ferroptosis is an iron-dependent form of cell death driven by peroxidation of phospholipids with polyunsaturated fatty acyl (PUFA) tails. Dietary factors, such as fatty acids and iron, regulate ferroptosis. Moreover, the incidence and progression of several cancers is correlated with diet; models of lymphoma have shown sensitivity to ferroptosis.

We investigated the effects of altering dietary factors linked to ferroptosis on diffuse large B cell lymphomas (DLBCL). We found that DLBCL cells undergo ferroptosis in response to iron and PUFA treatments in vitro, and that their growth in xenograft models is substantially reduced. We observed that monounsaturated fatty acids (MUFAs), in contrast, suppress ferroptosis and promote growth in DLBCL cell and animal models. The inhibitory effect of the ferroptosis inducer imidazole ketone erastin (IKE) on DLBCL xenograft growth was lessened by dietary MUFA. Ferroptosis linked fatty acids and iron thus impact the growth and response to ferroptosis treatment of DLBCL tumors.