Induction of the cholesterol biosynthesis pathway in differentiated Caco-2 cells by the potato glycoalkaloid alpha-chaconine.
Glycoalkaloids are naturally occurring toxins in potatoes, which at high levels may induce toxic effects in humans, mainly on the gastrointestinal tract by cell membrane disruption. In order to better understand the molecular mechanisms underlying glycoalkaloid toxicity, we examined the effects of alpha-chaconine on gene expression in the Caco-2 intestinal epithelial cell line using DNA microarrays. Caco-2 cells were exposed for 6h to 10 microM alpha-chaconine in three independent experiments (randomized block design). The most prominent finding from our gene expression and pathway analyses was the upregulation of expression of several genes involved in cholesterol biosynthesis. This to some extent is in line with the literature-described mechanism of cell membrane disruption by glycoalkaloids. In addition, various growth factor signaling pathways were found to be significantly upregulated. This study is useful in understanding the mechanism(s) of alpha-chaconine toxicity, which may be extended to other potato glycoalkaloids more generally.
Mandimika
Tafadzwa
T
RIKILT - Institute of Food Safety, Wageningen University and Research Centre, P.O. Box 230, 6700 AE Wageningen, The Netherlands.
Baykus
Hakan
H
Poortman
Jenneke
J
Garza
Cutberto
C
Kuiper
Harry
H
Peijnenburg
Ad
A
D015415:Biomarkers; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D002784:Cholesterol / Q000096:biosynthesis*; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012992:Solanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011198:Solanum tuberosum / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects
D015415:Biomarkers; D012992:Solanine; C011860:alpha-chaconine; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase