Differential Gene Expression in Intestinal Epithelial Cells Induced by Single and Mixtures of Potato Glycoalkaloids

• Published in: Journal of agricultural and food chemistry Vol. 55; no. 24; pp. 10055 - 10066
• Main Authors: Mandimika, Tafadzwa, Baykus, Hakan, Vissers, Yvonne, Jeurink, Prescilla, Poortman, Jenneke, Garza, Cutberto, Kuiper, Harry, Peijnenburg, Ad
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 28.11.2007
• Subjects: alpha-chaconine; antinutritional factors; apoptosis; Apoptosis - drug effects; biochemical pathways; Biological and medical sciences; Caco-2 Cells - drug effects; cell cycle; Cell Cycle - drug effects; cell membrane disruption; cell membranes; cholesterol; Cholesterol - biosynthesis; cultured cells; DNA microarrays; Dose-Response Relationship, Drug; epithelial cells; Food industries; Fruit and vegetable industries; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression Profiling; glycoalkaloids; Humans; intestinal mucosa; Intestinal Mucosa - cytology; L-Lactate Dehydrogenase - drug effects; lipid metabolism; Lipid Metabolism - drug effects; microarray technology; Oligonucleotide Array Sequence Analysis; potatoes; Proteins - metabolism; Safety/Toxicology; Severity of Illness Index; solanine; Solanine - analogs & derivatives; Solanine - analysis; Solanine - pharmacology; Solanum tuberosum; Solanum tuberosum - chemistry; transcription (genetics); α-Chaconine; α-solanine; DNA microarrays; glycoalkaloids; potatoes; α-solanine; α-Chaconine; cell membrane disruption; Vegetables; Solanine; Gene expression; Mixture; Potato; Alkaloid; DNA; Tuber; Epithelial cell; Membrane; Disruption
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf0724320

α-Chaconine and α-solanine are naturally occurring toxins. They account for 95% of the total glycoalkaloids in potatoes (Solanum tuberosum L.). At high levels, these glycoalkaloids may be toxic to humans, mainly by disrupting cell membranes of the gastrointestinal tract. Gene-profiling experiments were performed, whereby Caco-2 cells were exposed to equivalent concentrations (10 µM) of pure α-chaconine or α-solanine or glycoalkaloid mixtures of varying α-chaconine/α-solanine ratios for 6 h. In addition, lactate dehydrogenase, cell cycle, and apoptosis analyses experiments were also conducted to further elucidate the effects of glycoalkaloids. The main aims of the study were to determine the transcriptional effects of these glycoalkaloid treatments on Caco-2 cells and to investigate DNA microarray utility in conjunction with conventional toxicology in screening for potential toxicities and their severity. Gene expression and pathway analyses identified changes related to cholesterol biosynthesis, growth signaling, lipid and amino acid metabolism, mitogen-activated protein kinase (MAPK) and NF-κB cascades, cell cycle, and cell death/apoptosis. To varying extents, DNA microarrays discriminated the severity of the effect among the different glycoalkaloid treatments.