Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.565524
Keywords
falcarindiol; lipid droplets; cholesteryl esters; PPAR gamma; ABCA1; colorectal cancer; type 2 diabetes; Raman spectroscopy
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Funding
- Carlsberg foundation [CF14-0786]
- Villum Kann Rasmussen foundation [19105]
- Independent Research Fund Denmark Project [7017-00163]
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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 PPAR gamma 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 mu M) 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 PPAR gamma 2 as shown in human colon adenocarcinoma cells. Activation of PPAR gamma 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.
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