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The anticancer activity of alpha-tomatine against mammary adenocarcinoma in mice
P. Tomsik, S. Micuda, L. Sucha, E. Cermakova, P. Suba, P. Zivny, Y. Mazurova, J. Knizek, M. Niang, M. Rezacova
Jazyk angličtina Země Česko
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Directory of Open Access Journals
od 2001
Free Medical Journals
od 1998
Medline Complete (EBSCOhost)
od 2007-06-01
ROAD: Directory of Open Access Scholarly Resources
od 2001
PubMed
23681309
DOI
10.5507/bp.2013.031
Knihovny.cz E-zdroje
- MeSH
- bilirubin krev MeSH
- biologické markery metabolismus MeSH
- doxorubicin aplikace a dávkování MeSH
- Ehrlichův tumor farmakoterapie metabolismus MeSH
- experimentální nádory mléčných žláz farmakoterapie metabolismus MeSH
- játra účinky léků MeSH
- myši MeSH
- proliferace buněk účinky léků MeSH
- protinádorová antibiotika aplikace a dávkování MeSH
- tomatin aplikace a dávkování analogy a deriváty farmakologie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIM: 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.
Citace poskytuje Crossref.org
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- $a AIM: 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.
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