Poly-Unsaturated Fatty Acids (PUFAs) from Cunninghamella elegans Grown on Glycerol Induce Cell Death and Increase Intracellular Reactive Oxygen Species

Abstract

Cunninghamella elegans NRRL-1393 is an oleaginous fungus able to synthesize and accumulate unsaturated fatty acids, amongst which the bioactive gamma-linolenic acid (GLA) has potential anti-cancer activities. C. elegans was cultured in shake-flask nitrogen-limited media with either glycerol or glucose (both at ≈60 g/L) employed as the sole substrate. The assimilation rate of both substrates was similar, as the total biomass production reached 13.0–13.5 g/L, c. 350 h after inoculation (for both instances, c. 27–29 g/L of substrate were consumed). Lipid production was slightly higher on glycerol-based media, compared to the growth on glucose (≈8.4 g/L vs. ≈7.0 g/L). Lipids from C. elegans grown on glycerol, containing c. 9.5% w/w of GLA, were transformed into fatty acid lithium salts (FALS), and their effects were assessed on both human normal and cancerous cell lines. The FALS exhibited cytotoxic effects within a 48 h interval with an IC50 of about 60 μg/mL. Additionally, a suppression of migration was shown, as a significant elevation of oxidative stress levels, and the induction of cell death. Elementary differences between normal and cancer cells were not shown, indicating a generic mode of action; however, oxidative stress level augmentation may increase susceptibility to anticancer drugs, improving chemotherapy effectiveness.

Poly-unsaturated Fatty Acids fromThamnidium elegansandMortierella alpinaSuppress Prostate Cancer Cells Proliferation and Migration

“…The effects of EPA concentrate were even greater, causing an 80% reduction in cell migration, while the use of olive oil FALS at the same concentration only reduced migration by 40-50% in both cell lines, which was significantly lower compared to the microbial-derived FALS. These observations, emphasize the potential antitumor activity GLA-, DHGLA-, and ARA-rich lipids can exhibit and support the further use of lithium salts (FALS) as a way to administer them as has already been shown by previous studies (Alakhras et al ., 2015; Sayegh et al ., 2016; Kalampounias et al ., 2024).…”

“…This form is a liquid, water-soluble compound that does not require further transformations to be assimilable (e.g. the formation of liposomes or micelles) and has already been found to cause cell death by causing oxidative damage, and inducting apoptosis (Alakhras et al ., 2015; Sayegh et al ., 2016; Kalampounias et al ., 2024). Given the variety of different fatty acids that can be produced through fermentation, it is important to recognize both the molecules possessing increased medicinal interest as well as to invest in the optimization of the culture process to achieve better yields and use more cost-effective strategies.…”

“…The O.D. values were converted to cell numbers using standard curves as described in previous studies (Kalampounias et al ., 2024).…”

Impact of Plant Oil Supplementation on Lipid Production and Fatty Acid Composition in Cunninghamella elegans TISTR 3370

“…Among these, polyunsaturated fatty acids (PUFAs) play crucial roles in higher eukaryotes as energy stores and membrane constituents [3,4]. Their biological activities make them potential candidates for food additives or pharmaceuticals, with applications in the treatment of cardiovascular disorders, cancer, inflammatory reactions, liver lipid disorders, and postpartum mental health [1,[5][6][7][8][9]. Unlike other organisms, humans are unable to synthesize PUFAs in sufficient quantities, necessitating their acquisition through dietary sources [10,11].…”

“…Further PUFA synthesis requires desaturation mediated by ∆6 desaturase of appropriate fatty acid precursors, followed by chain elongation and additional desaturation steps, ultimately yielding C20 and C22 PUFAs [2,[15][16][17]. Among the fungi, species of the Cunninghamella genus, belonging to the oleaginous Zygomycetes, have been utilized for the production of PUFA-rich lipids such as γ-linolenic acid (GLA) [6,[18][19][20]. The Mucoralean fungus C. elegans CFR C07 has emerged as a promising source of γ-linolenic acid (GLA), exhibiting a preference for glucose as the primary carbon source under submerged conditions, while fructose and sucrose have demonstrated efficacy in biomass production.…”