Using punicic acid to potentialize the effect of anti-cancer drugs on prostate cancer cells

Details

Supervisors

Larondelle, Yvan ; Vermonden, Perrine

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en sciences agronomiques, à finalité spécialisée

Abstract

Conjugated linolenic acids (CLnAs), which are fatty acids containing a conjugated system of 3 double bonds, are interesting fatty acids, in particular for their cytotoxic effect on cancer cells. It has been shown that CLnAs induce a caspase-independent cell death, which is called ferroptosis. Prostate cancer, which is an uncontrolled growth of epithelial cells of the prostate lining, is the second most common cancer in men. The main treatments when prostate cancer is potentially metastatic are androgen deprivation therapy (ADT) and chemotherapy. Targeted therapy can also be used in specific cases. In addition to these therapeutic approaches, ferroptosis is emerging as a promising way to target cancer cells, in particular the therapy-resistant and metastatic ones. Earlier work in our lab has shown that two prostate cancer cell lines, 22Rv1 and PC-3, are sensitive to punicic acid (PunA), a CLnA isomer. Knowing the potential treatments that exist to fight prostate cancer and the sensitivity of these two prostate cell lines to PunA, the main aim of this master’s thesis is to determine if PunA can be used to potentialize the effect of anti-cancer drugs on prostate cancer cells. PunA had a synergistic effect, depending on the prostate cancer cell lines, with Enzalutamide, a second-generation ADT compound, and with FIN56 and IKE, two ferroptosis inducers, on a 2D cell culture model. In contrast, PunA did not have a synergistic effect with Bicalutamide, a the first generation ADT compound, Docetaxel and Mitoxantrone, two chemotherapeutic compounds and Olaparib, a targeted therapy compound, on a 2D cell culture model. The synergy between PunA and ferroptosis inducers was further confirmed in 22Rv1-derived spheroids, with a reduction in their growth and viability when ferroptosis inducers were combined with PunA. This synergistic effect was less clear in terms of lipid peroxidation levels. Some experiment parameters, such as the period of treatment and concentrations of ferroptosis inducers, still need to be adjusted to allow the synergistic effect between ferroptosis inducers and PunA to be better demonstrated. To further understand the mechanisms explaining the synergism between ferroptosis inducers and PunA, it would be interesting to measure the expression and activity of ferroptosis-related proteins, under the action of ferroptosis inducers, combined or not with PunA. The present master’s thesis has highlighted the role of PunA as a potentializer of ferroptosis inducers. Further in vivo investigations would be interesting in order to validate this property and determine if ferroptosis could represent a liable target to fight against prostate cancer.