A rare eicosanoid precursor analogue, sciadonic acid (5Z,11Z,14Z-20:3), detected in vivo in hormone positive breast cancer tissue

H G Park; J Y Zhang; C Foster; D Sudilovsky; D A Schwed; J Mecenas; S Devapatla; P Lawrence; K S D Kothapalli; J T Brenna

doi:10.1016/j.plefa.2018.05.002

A rare eicosanoid precursor analogue, sciadonic acid (5Z,11Z,14Z-20:3), detected in vivo in hormone positive breast cancer tissue

Prostaglandins Leukot Essent Fatty Acids. 2018 Jul:134:1-6. doi: 10.1016/j.plefa.2018.05.002. Epub 2018 May 16.

Authors

H G Park¹, J Y Zhang², C Foster³, D Sudilovsky³, D A Schwed³, J Mecenas³, S Devapatla³, P Lawrence⁴, K S D Kothapalli⁵, J T Brenna⁶

Affiliations

¹ Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Dell Pediatric Research Institute and Dept. of Pediatrics, Dell Medical School, The University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX 78723, USA.
² Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
³ Cayuga Medical Center, 101 Dates Drive, Ithaca, NY 14850, USA.
⁴ Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
⁵ Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Dell Pediatric Research Institute and Dept. of Pediatrics, Dell Medical School, The University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX 78723, USA. Electronic address: kkothapalli@utexas.edu.
⁶ Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Dell Pediatric Research Institute and Dept. of Pediatrics, Dell Medical School, The University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX 78723, USA; Department of Chemistry, The University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, TX 78723, USA. Electronic address: tbrenna@utexas.edu.

Abstract

Numerous genetic alterations of HSA 11q13 are found frequently in several cancer types, including breast cancer (BC). The 11q13 locus harbors FADS2 encoding Δ6 desaturation which is not functional in several cancer cell lines, including hormone positive MCF7 BC cells. In vitro, the non-functional FADS2 activity unmasks 18:2n-6 elongation to 20:2n-6 and Δ5 desaturation by FADS1 to yield 5Z,11Z,14Z-20:3 (sciadonic acid) rather than 5Z,8Z,11Z,14Z-20:4 (arachidonic acid). In this pilot study we aimed to determine whether 5,11,14-20:3 appears in vivo in hormone positive human BC tissue. Fatty acids were profiled in surgically removed human breast tumor and adjacent normal tissue (n = 9). Sciadonic acid was detected in three of nine breast tumor samples and was below detect limits in normal breast tissue. The internal Δ8 double bond of arachidonic acid is required for normal eicosanoid synthesis but is missing in sciadonic acid. This pilot study demonstrates for the first time in vivo sciadonic acid in hormone positive BC tissue, warranting a larger survey study to further evaluate its appearance and the functional implications.

Keywords: Breast cancer; Cell signaling; Docosanoid; Eicosanoid; Estrogen; Fatty acid desaturase 2.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Arachidonic Acids / analysis*
Breast / chemistry
Breast Neoplasms / chemistry*
Breast Neoplasms / genetics
Breast Neoplasms / surgery*
Chromatography, Gas
Delta-5 Fatty Acid Desaturase
Fatty Acid Desaturases / genetics
Female
Humans
MCF-7 Cells
Mastectomy / methods
Mice
Pilot Projects
Swiss 3T3 Cells

Substances

Arachidonic Acids
Delta-5 Fatty Acid Desaturase
eicosa-5,11,14-trienoic acid
Fatty Acid Desaturases
FADS1 protein, human
FADS2 protein, human

Grants and funding

R01 AT007003/AT/NCCIH NIH HHS/United States