TY - JOUR
T1 - Falcarindiol Purified from Carrots Leads to Elevated Levels of Lipid Droplets and Upregulation of Peroxisome Proliferator-Activated Receptor-γ Gene Expression in Cellular Models
AU - Andersen, Camilla Bertel
AU - Runge Walther, Anders
AU - Pipó-Ollé, Emma
AU - K. Notabi, Martine
AU - Juul, Sebastian
AU - Eriksen, Mathias Hessellund
AU - Lovatt, Adam Leslie
AU - Cowie, Richard Henry
AU - Linnet, Jes
AU - Kobæk Larsen, Morten
AU - El-Houri, Rime
AU - Andersen, Morten Østergaard
AU - Hedegaard, Martin A.B.
AU - Christensen, Lars Porskjær
AU - Arnspang, Eva C.
PY - 2020/8/28
Y1 - 2020/8/28
N2 - Falcarindiol (FaDOH) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae). FaDOH has been shown to activate PPARγ and to increase the expression of the cholesterol transporter ABCA1 in cells, both of which play an important role in lipid metabolism. Thus, a common mechanism of action of the anticancer and antidiabetic properties of FaDOH may be due to a possible effect on lipid metabolism. In this study, the effect of sub-toxic concentration (5 μM) of FaDOH inside human mesenchymal stem cells (hMSCs) was studied using white light microscopy and Raman imaging. Our results show that FaDOH increases lipid content in the hMSCs cells as well as the number of lipid droplets (LDs) and that this can be explained by increased expression of PPARγ2 as shown in human colon adenocarcinoma cells. Activation of PPARγ can lead to increased expression of ABCA1. We demonstrate that ABCA1 is upregulated in colorectal neoplastic rat tissue, which indicates a possible role of this transporter in the redistribution of lipids and increased formation of LDs in cancer cells that may lead to endoplasmic reticulum stress and cancer cell death.
AB - Falcarindiol (FaDOH) is a cytotoxic and anti-inflammatory polyacetylenic oxylipin found in food plants of the carrot family (Apiaceae). FaDOH has been shown to activate PPARγ and to increase the expression of the cholesterol transporter ABCA1 in cells, both of which play an important role in lipid metabolism. Thus, a common mechanism of action of the anticancer and antidiabetic properties of FaDOH may be due to a possible effect on lipid metabolism. In this study, the effect of sub-toxic concentration (5 μM) of FaDOH inside human mesenchymal stem cells (hMSCs) was studied using white light microscopy and Raman imaging. Our results show that FaDOH increases lipid content in the hMSCs cells as well as the number of lipid droplets (LDs) and that this can be explained by increased expression of PPARγ2 as shown in human colon adenocarcinoma cells. Activation of PPARγ can lead to increased expression of ABCA1. We demonstrate that ABCA1 is upregulated in colorectal neoplastic rat tissue, which indicates a possible role of this transporter in the redistribution of lipids and increased formation of LDs in cancer cells that may lead to endoplasmic reticulum stress and cancer cell death.
KW - ABCA1
KW - PPARγ
KW - Raman spectroscopy
KW - cholesteryl esters
KW - colorectal cancer
KW - falcarindiol
KW - lipid droplets
KW - type 2 diabetes
U2 - 10.3389/fphar.2020.565524
DO - 10.3389/fphar.2020.565524
M3 - Journal article
C2 - 32982759
SN - 1663-9812
VL - 11
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 565524
ER -