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This study first investigates the anti-metastatic effect of alpha-tomatine in the human lung adenocarcinoma cell line: A549. In this study, we first noted alpha-tomatine inhibited A549 cells invasion and migration by wound-healing assay and Boyden chamber assay. The data also showed alpha-tomatine could inhibit phosphorylation of Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2), which is involved in the up-regulating matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) or urokinase-type plasminogen activator (u-PA), whereas it did not affect phosphorylation of c-Jun N-terminal kinase (JNK) and p38. Next, alpha-tomatine significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, treating A549 cells with alpha-tomatine also leads to a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1). Further, the treatment of inhibitors specific for PI3K (Wortmannin) or ERK (U0126) to A549 cells could cause reduced activities of MMP-2, MMP-9, and u-PA. These results showed alpha-tomatine could inhibit the metastatic ability of A549 cells by reducing MMP-2, MMP-9, and u-PA activities through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) or ERK1/2 signaling pathway and inhibition NF-kappaB or AP-1 binding activities. These findings proved alpha-tomatine might be an anti-metastatic agent against human lung adenocarcinoma.

Tomatoes contain the steroidal glycoalkaloid tomatine, which has been reported to form strong, insoluble complexes with cholesterol in vitro. To determine whether tomatine can reduce dietary cholesterol absorption and plasma levels of cholesterol and triglycerides, we fed hamsters a high-fat, high-cholesterol diet with 0.05-0.2% added tomatine in the diet. The tomatine diets induced lowering of serum low-density lipoprotein (LDL) without changing high-density lipoprotein (HDL) cholesterol. Compared to the control diets, four- to fivefold more labeled dietary cholesterol and coprostanol was excreted in the feces of the tomatine-fed hamsters. The amount of cholesterol excreted in the feces corresponded to the amount of tomatine in the diet. These observations suggest that due to the formation of an insoluble tomatine-cholesterol complex and its excretion in the feces, very little dietary tomatine is absorbed from the digestive tract into the blood stream. They are also consistent with the reported low oral toxicity of tomatine compared to other glycoalkaloids.

alpha-Tomatine, a glycoside in which four carbohydrate residues are attached to the 3-OH group of the aglycone tomatidine, occurs naturally in tomatoes (Lycopersicon esculentum). The glycoalkaloid is reported to be involved in host-plant resistance against phytopathogens and to have a variety of pharmacological and toxicological properties in animals and humans. As part of an effort designed to establish the mechanism of action of glycoalkaloids in cells, frog embryos and frog skin were exposed to varying concentrations of alpha-tomatine and tomatidine. alpha-Tomatine increased the fluorescence-measured membrane permeability of frog embryos by about 600% compared with control values; the corresponding value for tomatidine was about 150%. alpha-Tomatine also diminished sodium-active transport in frog skin by about 16% compared with control values, as estimated from the change in the interstitial short-circuit current. Tomatidine had no effect on frog skin. As these findings complement similar results with glycoalkaloids from potatoes and eggplants, the fundamental mechanism governing their action both against fungi, insects and other phytopathogens and in animal and human cells may be disruption of cell membranes and changes in ion fluxes and interstitial currents of the membranes. The described methodologies should make it possible to define the relative potencies of both adverse and beneficial effects of glycoalkaloids and metabolites in cell membranes without the use of animals.