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 p21 WAF1/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.
- Keywords
- chk2, checkpoint kinase 2,
- MeSH
- Apoptosis drug effects MeSH
- Cell Death drug effects MeSH
- Comet Assay MeSH
- Leukemia, T-Cell * drug therapy MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 * analysis metabolism drug effects MeSH
- Oncogene Protein p21(ras) MeSH
- DNA Damage MeSH
- Cell Proliferation drug effects MeSH
- Protein Serine-Threonine Kinases metabolism MeSH
- Antineoplastic Agents MeSH
- Flow Cytometry MeSH
- Puma MeSH
- DNA Replication MeSH
- Statistics as Topic MeSH
- In Vitro Techniques MeSH
- Tomatine * analogs & derivatives therapeutic use MeSH
- Blotting, Western MeSH
Using ITS2 gene sequences, the validity of the tapeworm Diphyllobothrium pacificum (Nybelin, 1931), infecting humans on the Pacific coast of South America and in Japan, was assessed. ITS2 sequences of this cestode differed markedly (sequence similarity 79.0-80.2%) from those of the most common human-infecting cestode, the broad fish tapeworm Diphyllobothrium latum (L.), as well as other four species of Diphyllobothrium, including potential human parasites (D. cordatum, D. dendriticum, and D. lanceolatum) and two species of Spirometra (sequence similarity 77.5-81.9%). Interspecific sequence similarity between all but one (D. pacificum) species was 86.1-99.6%, whereas individual isolates of D. dendriticum and D. ditremum exhibited intraspecific sequence similarity of 97.0-98.0% and 98.2-99.9%, respectively. Phylogenetic trees constructed from ITS2 sequences show a markedly distant position of D. pacificum from other species analyzed and also indicate the possible paraphyly of Spirometra.
- MeSH
- Diphyllobothriasis parasitology MeSH
- Diphyllobothrium genetics classification MeSH
- Financing, Organized MeSH
- Phylogeny MeSH
- Herpestidae MeSH
- Fur Seals MeSH
- Humans MeSH
- DNA, Ribosomal Spacer genetics MeSH
- Molecular Sequence Data MeSH
- Walruses MeSH
- Puma MeSH
- Fishes MeSH
- Sequence Homology, Nucleic Acid MeSH
- Geography MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
- Geographicals
- South America MeSH