Punicic acid, a trojan horse to induce ferroptosis in prostate cancer cells
(2022) ParadOx Meeting : the good and the bad sides of oxidation — Location: Bruxelles, Woluwé (20.May.2022)
Files
No attached file found for this publication.
Details
- Authors
- et. al.
- Abstract
- Ferroptosis is a recently discovered form of regulated cell death that is executed through extensive polyunsaturated fatty acid (PUFA) peroxidation, the presence of redox-active iron and a defective lipid peroxide repair. Multiple drugs have already been identified as ferroptosis inducers in cancer cells. Another strategy, yet largely unexplored, may lie in the promotion of lipid peroxidation by preferentially introducing high amounts of peroxidable PUFA in cancer cells. We propose here that plant-derived conjugated linolenic acids (CLnA) represent an attractive PUFA source to promote ferroptosis. Due to the conjugated configuration of their three double bonds, CLnA are much more peroxidation-prone than non-conjugated PUFA. Recently, our team has shown that punicic acid (PunA), a CLnA isomer, acts as a strong ferroptosis inducer in carcinoma cells. Taking advantage of the high dependency of prostate cancer cells on fatty acid metabolism, we have compared the ferroptosis-sensitizing potential of PunA in prostate cancer cells. Androgen-negative therapy-resistant prostate cancer cells were more sensitive than androgen-positive cells (i.e. IC50 of 1.5 µM versus 14 µM, respectively). PunA toxicity was further enhanced by inhibition of either ß-oxidation or lipid droplet incorporation, two protective mechanisms diverting PUFA from peroxidation-prone species. PunA differential effects were further supported by reduced expression in androgen-negative cells, of enzymes involved in PUFA incorporation into phospholipids and lipid peroxide cellular detoxification. Lipidomic analysis also revealed that PunA uptake and incorporation within cellular lipid species are increased by two-fold in the most sensitive cells. Altogether, our findings reveal critical redox metabolic differences in prostate cancer cell subtypes that may be used to select the most ferroptosis-sensitive ones.
- Affiliations
Citations
Vermonden, P., & et al. (2022). Punicic acid, a trojan horse to induce ferroptosis in prostate cancer cells. ParadOx Meeting : the good and the bad sides of oxidation, Bruxelles, Woluwé. https://hdl.handle.net/2078.5/105752