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

Alpha-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 μmol/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. © journal of applied biomedicine.