Oxidized Products of α-Linolenic Acid Negatively Regulate Cellular Survival and Motility of Breast Cancer Cells.

Jorge L Gutierrez-Pajares,Jean-Marie Galano,Celine Ben Hassen,Philippe G Frank,Camille Oger,Thierry Durand

doi:10.3390/biom10010050

Abstract

Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively. In this work, seven PhytoPs (PP1–PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization, and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines. Among the tested compounds, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability of MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs displayed significantly enhanced cytotoxic effects on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells. In addition, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.

Highlights

Cancer is a major cause of death in the world, and while 18.1 million new cases are expected to be detected in 2018, 9.6 million cancer-related deaths may occur [1]
In the first series of experiments, we analyzed their effects on cellular survival in the presence of 1% fetal bovine serum (FBS) for 48 h (Figure 2A)
PP7 reduced the survival of MCF-7 cells, while PP5 and PP6 had similar effects on MDA-MB-231 cells and Interestingly, PP7 reduced the survival of MCF-7 cells,the while

Summary

Introduction

Cancer is a major cause of death in the world, and while 18.1 million new cases are expected to be detected in 2018, 9.6 million cancer-related deaths may occur [1]. Despite recent advances in our understanding of the biological processes leading to the development of cancer, there is still a need for new and effective methods of treatment for this disease. Natural products and their derivatives represent an important source of new therapeutic agents, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically effective anti-cancer agents [2]. A number of anticancer agents derived from plants have been identified, many compounds that may exhibit anti-cancer properties remain to be identified. Arachidonate (ARA, C20:4 n-6) may be transformed via a non-enzymatic oxidative cyclization

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Discussion

Conclusion