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Neoplasma Vol.52, p.425-429, 2004 |
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Title: Cytotoxic activity of a podophyllotoxin-like lignan from Linum tauricum Willd | ||
Author: N., VASILEV ; G., MOMEKOV ; M., ZAHARIEVA ; S., KONSTANTINOV ; P., BREMNER ; M., HEINRICH ; I., IONKOVA ; | ||
Abstract: The present study describes the preliminary evaluation of the cytotoxic activity of a podophyllotoxin-like compound
4’-demethyl-6-methoxypodophyllotoxin (4’-DM-6-Mptox), isolated as one of the main lignans of Linum tauricum Willd.
ssp. tauricum. The cytotoxic effects 4’-DM-6-Mptox were assessed by the MTT-dye reduction assay against the human leukemic
cell lines HL-60, BV-173 and LAMA-84. DNA-fragmentation analysis and NF-kB inhibition assay were performed
in order to elucidate some of the mechanistic aspects of the cytotoxic action of the investigated compound. 4’-DM-6-Mptox
was found to exert prominent cytotoxicity, with IC50 values being several-fold lower than those of the referent antineoplastic
agent etoposide. The DNA-fragmentation analysis revealed that 4’-DM-6-Mptox treatment triggered apoptosis in BV-173
and HL-60 cells. In our hands 4’-DM-6-Mptox was found to induce concentration-dependent NF-kB inhibition in HeLa
cells as assessed by the IL-6 luciferase gene reporter assay, which though not quite prominent, at least partly contributes to
the cytotoxic potential of the tested lignan. On the basis of the results obtained it could be concluded that 4’-DM-6-Mptox
necessitates further pharmacological and toxicological evaluation as a possible chemotherapeutic agent. Furthermore due to
its relatively high concentrations in the described plant source the possibility for its use as a precursor for the semisynthetic
production of lignan-based drugs, could be considered.
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Keywords: 4’-demethyl-6-methoxypodophyllotoxin, lignans, Linum tauricum Willd. ssp. tauricum, cytotoxicity, apoptosis, NF-k-B inhibition | ||
Year: 2004, Volume: 52, Issue: | Page From: 425, Page To: 429 | |
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