Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes

Abstract

Background: Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models. Objective: The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far. Methods: We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways. Results: The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studies: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased p-P44/42 MAPK levels, and increased EGFR levels. Conclusion: Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.

Cytotoxicity Effects of Vitamin C on Cancer Cells MCF-7

“…Another study that used a combination of vitamin C with somatostatin on MCF-7 and MDA-MB231 breast cancer cells caused membrane remodeling in MCF-7 cells that could affect signaling processes. In MCF-7 cells the combination of vitamin C and somatostatin significantly decreased EGFR (Epidermal Growth Factor Receptors) and MAPK (Mitogen-Activated Protein Kinase) signaling compared to MDA-MB231 cells (Hanikoglu et al, 2019).…”

“…It was reported that this cytotoxic effect is related to the pro-oxidant properties of vitamin C, which can activate the transcription factor NF-kappa B and inhibit cell growth. In addition, by producing hydrogen peroxide and activating hydroxyl radicals, vitamin C can reduce cell replication mechanisms and cancer cell viability by inducing DNA strand damage, controlling mitotic activity, and damaging mitochondria and cell membranes (Lee, 2009;Gonzales et al, 2014).…”

“…Based on the list of essential drugs according to WHO, vitamin C is generally used as one of the most important dietary supplements and as a drug that is safe for the body's health. This antioxidant supplement plays an important role in the process of tissue repair, produces neurotransmitters through enzymatic mechanisms, and modulates the immune system (Gonzales et al, 2014).…”

“…It has been further demonstrated that the cytotoxic effect of vitamin C on cancer cells is related to its prooxidant properties caused inhibition of cell growth and reduces the replication mechanism and viability of cancer cells or tumor cells. Vitamin C can act as an anticancer agent because it can cause cancer cell death through the stabilization of p53 protein (Gonzales et al, 2014). Further studies reported that combining vitamin C with 5-fluorouracil, sodium d-ascorbate, cyclophosphamide, paclitaxel, arsenic trioxide, doxorubicin, and radiation could sensitize cancer cells to anticancer drugs and increase the success rate of chemotherapy or radiotherapy.…”

“…High doses of vitamin C in breast cancer cells are cytotoxic to MCF7 and MDA-MB231 cells (Melzer et al, 2021). In its use, vitamin C can be combined with Somatostatin, a natural peptide that has a growth inhibitory effect in several breast cancer models (Hanikoglu et al, 2019).…”