α-Tomatine-Mediated Anti-Cancer Activity In Vitro and In Vivo through Cell Cycle- and Caspase-Independent Pathways
Journal
PLoS ONE
Journal Volume
7
Journal Issue
9
Date Issued
2012
Author(s)
Abstract
α-Tomatine, a tomato glycoalkaloid, has been reported to possess antibiotic properties against human pathogens. However, the mechanism of its action against leukemia remains unclear. In this study, the therapeutic potential of α-tomatine against leukemic cells was evaluated in vitro and in vivo. Cell viability experiments showed that α-tomatine had significant cytotoxic effects on the human leukemia cancer cell lines HL60 and K562, and the cells were found to be in the Annexin V-positive/propidium iodide-negative phase of cell death. In addition, α-tomatine induced both HL60 and K562 cell apoptosis in a cell cycle- and caspase-independent manner. α-Tomatine exposure led to a loss of the mitochrondrial membrane potential, and this finding was consistent with that observed on activation of the Bak and Mcl-1 short form (Mcl-1s) proteins. Exposure to α-tomatine also triggered the release of the apoptosis-inducing factor (AIF) from the mitochondria into the nucleus and down-regulated survivin expression. Furthermore, α-tomatine significantly inhibited HL60 xenograft tumor growth without causing loss of body weight in severe combined immunodeficiency (SCID) mice. Immunohistochemical test showed that the reduced tumor growth in the α-tomatine-treated mice was a result of increased apoptosis, which was associated with increased translocation of AIF in the nucleus and decreased survivin expression ex vivo. These results suggest that α-tomatine may be a candidate for leukemia treatment. ? 2012 Chao et al.
SDGs
Other Subjects
apoptosis inducing factor; caspase; paclitaxel; protein Bak; protein mcl 1; protein mcl 1s; survivin; tomatine; unclassified drug; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; article; cancer inhibition; cell cycle; controlled study; down regulation; drug cytotoxicity; ex vivo study; human; human cell; immunohistochemistry; in vitro study; in vivo study; leukemia cell; mitochondrial membrane potential; mouse; nonhuman; promyelocytic leukemia; protein expression; protein secretion; protein transport; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Inducing Factor; Caspases; Cell Cycle; Cell Nucleus; Down-Regulation; Enzyme Activation; HL-60 Cells; Humans; Inhibitor of Apoptosis Proteins; K562 Cells; Membrane Potential, Mitochondrial; Mice; Mice, SCID; Neoplasm Proteins; Protein Transport; Signal Transduction; Tomatine; Xenograft Model Antitumor Assays; Lycopersicon esculentum; Mus
Type
journal article