Structure-activity relationships of α-, β(1)-, 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 high-performance 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 γ- and 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.

• Authors: Suk Hyun Choi, Jun-Bae Ahn, Nobuyuki Kozukue, Hyun-Jeong Kim, Yosuke Nishitani, Ling Zhang, Masashi Mizuno, Carol E Levin, Mendel Friedman
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 60 Issue 15 Pg. 3891-9 (Apr 18 2012) ISSN: 1520-5118 [Electronic] United States
• PMID: 22482398 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Plant Extracts
• tomatidine
• Tomatine

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Breast Neoplasms (drug therapy, physiopathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Solanum lycopersicum (chemistry)
• Male
• Molecular Structure
• Plant Extracts (chemistry, pharmacology)
• Prostate
• Prostatic Neoplasms (drug therapy, physiopathology)
• Stomach Neoplasms (drug therapy, physiopathology)
• Tomatine (analogs & derivatives, chemistry, pharmacology)