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

Anticancer Agents Med Chem. 2019;19(15):1899-1909. doi: 10.2174/1871520619666190930130732.

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 studied: 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.

Keywords: Somatostatin; Vitamin C; breast cancer; cell signaling; gas chromatography; membrane fatty acid profile..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acids / metabolism
  • Ascorbic Acid / metabolism*
  • Breast Neoplasms / metabolism*
  • Cell Extracts / chemistry
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Fatty Acids / metabolism*
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Unsaturated / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Lipids
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phospholipids / chemistry
  • Signal Transduction
  • Somatostatin / metabolism*
  • Stearic Acids / metabolism

Substances

  • Arachidonic Acids
  • Cell Extracts
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Lipids
  • Phospholipids
  • Stearic Acids
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • stearic acid
  • Somatostatin
  • Mitogen-Activated Protein Kinase Kinases
  • docosapentaenoic acid
  • Ascorbic Acid