Alpha-tomatine activates cell cycle checkpoints in the absence of DNA damage in human leukemic MOLT-4 cells

SummaryAlpha-tomatine is a major glycoalkaloid found in the roots, leaves, stems and fruit of tomatoes Lycopersicon esculentum. Recently, alpha-tomatine has been recognized as a potential anticancer drug. In the present study, we identified the signaling cascades involved in the antitumor effect of alpha-tomatine on MOLT-4 leukemic cells. Alpha-tomatine inhibited the proliferation and decreased the viability of MOLT-4 cells in a dose-dependent manner. An increase in the activity of caspases 9 and 3/7 was not observed. However, an increase in the amount of p53 and its phosphorylation on serine 15, as well as an increased amount of mitochondrial protein PUMA was detected 4 and 24 h after exposure to alpha-tomatine at a concentration of 1–3 μml/l. Inhibition of the proliferation of MOLT-4 cells by alpha-tomatine is also associated with an increase in p21WAF1/CIP1 and the activation of Chk2. The comet assay did not detect significant amounts of single or double DNA strand breaks in cells treated with alpha-tomatine at concentrations of 0.1–9 μmol/l. Our results thus contribute to the understanding of the anticancer action of alpha-tomatine.