title: The anticancer activity of alpha-tomatine against mammary adenocarcinoma in mice.
abstract: OBJECTIVE
  To evaluate the anticancer effect of alpha-tomatine (i.p.) either alone or in combination with doxorubicin (i.v.) in a mouse tumour model.
  
  
  METHODS
  We studied the effect of repeated alpha-tomatine (0.1 - 9 mg/kg) and/or doxorubicin (2 mg/kg) on the growth and mitotic activity of the solid Ehrlich tumour in vivo, as well as on the survival of the tumour-bearing mice.
  
  
  RESULTS
  Monotherapy with alpha-tomatine had a significant dose-dependent anticancer effect which peaked at 1 mg/kg. This was shown by both slowed tumour growth and reduced tumour cell proliferation. We also provide the first evidence that the combination alpha-tomatine (1 mg/kg) and doxorubicin (2 mg/kg) had a synergistic effect and significantly prolonged the survival of the mice. Neither alpha-tomatine nor doxorubicin influenced the infiltration of tumours with CD3+ lymphocytes; nor were we able to find an in vivo modulation of the key molecules of two regulatory pathways reported in vitro as the principal anti-cancer mechanisms of alpha-tomatine, i.e. iNOS and phosphorylated ERK2. However, alpha-tomatine still led to intracellular DNA inhibition and protein synthesis in Ehrlich tumour cells in a short-term culture ex vivo with IC50 values of 8.7 and 6.6 µM.
  
  
  CONCLUSIONS
  The results suggest that ΤΟΜ, especially in combination with doxorubicin, may be a promising agent for the treatment of malignant solid tumours. Despite growing knowledge of the mechanisms of ΤΟΜ action in cancer cells, most aspects remain unclear. Parallel organ toxicity, especially potential liver effects, requires careful attention when performing in vivo studies in the future.
authors.affiliation: Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Czech Republic. tomsikp@lfhk.cuni.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Tomsik
authors.forename: Stanislav
authors.initials: S
authors.lastname: Micuda
authors.forename: Lenka
authors.initials: L
authors.lastname: Sucha
authors.forename: Eva
authors.initials: E
authors.lastname: Cermakova
authors.forename: Petr
authors.initials: P
authors.lastname: Suba
authors.forename: Pavel
authors.initials: P
authors.lastname: Zivny
authors.forename: Yvona
authors.initials: Y
authors.lastname: Mazurova
authors.forename: Jiri
authors.initials: J
authors.lastname: Knizek
authors.forename: Mohamed
authors.initials: M
authors.lastname: Niang
authors.forename: Martina
authors.initials: M
authors.lastname: Rezacova
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D008099:Liver / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D014053:Tomatine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; C484751:alpha-tomatine; D014053:Tomatine; D004317:Doxorubicin; D001663:Bilirubin