Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes

Abstract

Breast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their EC50 concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of ω6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of ω3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of ω6 linoleic, arachidonic acids, and ω3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin.

Flavonoid and Non-Flavonoid Compounds of Autumn Royal and Egnatia Grape Skin Extracts Affect Membrane PUFA’s Profile and Cell Morphology in Human Colon Cancer Cell Lines

“…As regards the n-3 fatty acids pathway, no variation was observed. Hanikoglu A. et al found differences in the reorganization of fatty acids in cell membranes of two different breast cancer cell lines, MCF-7 and MDA-MB231, after treatment with somatostatin, curcumin, and quercetin, alone or in combination [ 14 ]. Cancer cells, according to the degree of differentiation, behave differently to treatment with drugs and/or natural compounds, and this feature could explain the different response of SW480 to treatment with GSEs, with respect to Caco2 cells.…”

“…There are several mechanisms of action through which grape polyphenols are able to inhibit the invasion and progression of metastasis [ 11 , 12 , 13 ]. These natural compounds can act on the structural components of the cytoskeleton, on cellular adhesions, and on the composition of the membrane fatty acids [ 11 , 14 ].…”

Potentiation of the Effect of Lonidamine by Quercetin in MCF-7 human breast cancer cells through downregulation of MMP-2/9 mRNA Expression

“…Previous studies have reported relatively higher doses or longer durations of exposure for both compounds in order to obtain a significant cytotoxic activity on breast cancer cells (Maurya & Vinayak 2019, Morais-Santos et al 2013; however, some studies have reported a relatively lower dose for quercetin. For instance, Hanikoglu et al 2020 reported the IC 50 value of quercetin as 73.63 µM and Niazvand et al 2019 reported it as 73.8 µM, both after 24 h of incubation (Hanikoglu et al 2020, Niazvand et al 2019. Overall data indicate that the doses we have used in our study are within the spectrum of doses used in the previous and/or recent studies.…”

Bioactive Compounds and Metabolites from Grapes and Red Wine in Breast Cancer Chemoprevention and Therapy

“…Fatty acid synthase inhibition by flavonoids has been reported and associated with modulation of cell growth and promotion of apoptosis [63]. Quercetin led MDA-MB-231 and MCF-7 cells to EGFR reduction and this signaling promoted fatty acid alterations, including fatty acid isomerization and free radicals production [64].…”