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Alpha-tomatine is a major glycoalkaloid found in the roots, leaves, stems and fruit of tomatoes Lycopersiconesculentum. Recently, alpha-tomatine has been recognized as a potential anticancer drug. In the presentstudy, we identified the signaling cascades involved in the antitumor effect of alpha-tomatine on MOLT-4leukemic cells. Alpha-tomatine inhibited the proliferation and decreased the viability of MOLT-4 cells ina 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 ofmitochondrial protein PUMA was detected 4 and 24 h after exposure to alpha-tomatine at a concentrationof 1–3 μmol/l. Inhibition of the proliferation of MOLT-4 cells by alpha-tomatine is also associated with anincrease in p21WAF1/CIP1 and the activation of Chk2. The comet assay did not detect significant amounts ofsingle 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

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