Home Neoplasma 2004 Neoplasma Vol.52, p.425-429, 2004

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.52, p.425-429, 2004

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.

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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