The Tomato Glycoalkaloid α-Tomatine Induces Caspase-Independent Cell Death in Mouse Colon Cancer CT-26 Cells and Transplanted Tumors in Mice

Tomatoes (Solanum lycopersicum) produce the bioactive glycoalkaloid alpha-tomatine. This study determined the effect of commercial alpha-tomatine on CT-26 colon cancer cells in vitro and in vivo in an intracutaneously transplanted mouse tumor. Cytotoxicity experiments showed that alpha-tomatine induces about 50% lysis of the colon cancer cells at 3.5 mu M after 24 h of treatment. Large proportions of cells were found to be in the annexin V (+)/propidium iodide (+) phase of cell death, implying late phase apoptotic/necrotic status. However, alpha-tomatine induced cell death in CT-26 cancer cells through caspase-independent signaling pathways. This conclusion was supported by Western blot analysis showing a localization of apoptosis-inducing mitochondrial protein (AIF) to the nucleus and down-regulation of survivin (an inhibitor of apoptosis) expression as well as failure to detect the active form of caspase-3, -8, and -9 produced by proteolytic cleavage in CT-26 cancer cells. Intraperitoneally administered alpha-tomatine (5 mg/kg body weight) also markedly inhibited growth of the tumor using CT-26 cancer cells without causing body and organ weight changes. The reduced tumor growth in the mice by 38% after 2 weeks was the result of increased caspase-independent apoptosis associated with increased nuclear translocation of AIF and decreased survivin expression in tumor tissues. alpha-Tomatine in pure form and in tomatine-rich green tomatoes might prevent colon cancer.