Structure–Activity Relationships of α-, β₁-, γ-, and δ-Tomatine and Tomatidine against Human Breast (MDA-MB-231), Gastric (KATO-III), and Prostate (PC3) Cancer Cells

Abstract

Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid α-tomatine resulted in the formation of four products with three, two, one, and zero carbohydrate side chains, which were separated by highperformance liquid chromatography (HPLC) and identified by thin-layer chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC 50 values (concentration that inhibits 50% of the cells under the test conditions) of the parent compound and the hydrolysates, isolated by preparative HPLC, against normal human liver and lung cells and human breast, gastric, and prostate cancer cells indicate that (a) the removal of sugars significantly reduced the concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3 prostate cancer cells were about 10 times more susceptible to inhibition by α-tomatine than the breast and gastric cancer cells or the normal cells, (c) the activity of α-tomatine against the prostate cancer cells was 200 times greater than that of the aglycone tomatidine, and (d) the activity increased as the number of sugars on the aglycone increased, but this was only statistically significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the alkaloids on tumor necrosis factor α (TNF-α) was measured in RAW264.7 macrophage cells. There was a statistically significant negative correlation between the dosage of γand α-tomatine and the level of TNF-α. α-Tomatine was the most effective compound at reducing TNF-α. The dietary significance of the results and future research needs are discussed.

Tomatoes protect against development of UV-induced keratinocyte carcinoma via metabolomic alterations

“…Both tomatidine and α-tomatine have been shown to be anti-carcinogenic in vitro 34, 35 and have in vivo biological effects (including inhibiting skeletal muscle atrophy and weakness 36, 37 and reducing plasma lipoprotein concentration 38 ), lending plausibility to the idea that these compounds could be at least partially responsible for the decreases in tumor number observed here. Other identities can be tentatively assigned via accurate mass, relative retention time and MS/MS fragmentation patterns.…”

Plasma Metabolomics Reveals Steroidal Alkaloids as Novel Biomarkers of Tomato Intake in Mice

“…Tomatidine shows bioactivity in vitro based on studies with breast and prostate cancer cells, although less potent than α‐tomatine . Tomatidine has been found to inhibit the invasion of human lung cancer cells in vitro at 20 μM and reduce inflammation in LPS‐induced macrophages at similar concentrations .…”

Chemistry and Anticarcinogenic Mechanisms of Glycoalkaloids Produced by Eggplants, Potatoes, and Tomatoes

“…In another study, we discovered that the activity of α-tomatine generally decreases upon removal of one or more of the four carbohydrate groups of the lycotetraose side chain. 76 …”