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BIBTEX RIS

Cytotoxic activity of naphthoquinones with special emphasis on juglone and its 5-O-methyl derivative

2010; Elsevier BV; Volume: 184; Issue: 3 Linguagem: Inglês

10.1016/j.cbi.2010.01.041

ISSN

1872-7786

Autores

Raquel Carvalho Montenegro, Ana Jérsia Araújo, Marı́a Teresa Molina, José Delano Barreto Marinho Filho, Danilo D. Rocha, Eulogio López-Montero, Marília Oliveira Fonseca Goulart, Edson S. Bento, Ana Paula Nunes Negreiros Alves, Cláudia Pessoa, Manoel Odorico de Moraes, Letícia V. Costa‐Lotufo,

Tópico(s)

Phytochemistry and biological activity of medicinal plants

Resumo

The cytotoxicity of nine naphthoquinones (NQ) was assayed against HL-60 (leukaemia), MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human cancer cell lines, and peripheral blood mononuclear cells (PBMC), as representatives of normal cells, after 72h of incubation. 5-Methoxy-1,4-naphthoquinone was the most active compound, showing IC(50) values in the range of 0.31 (1.7microM) in HL-60 to 0.88microg/mL (4.7microM) in SF-295 and IC(50) of 0.69microg/mL (3.7microM) against PBMC. With the introduction of a bromo-substituent in position 2 or 3 of juglone, the IC(50) significantly decreased, regardless of the position on the NQ moiety. However, compared with juglone methyl ether, the halogen substitution decreased the activity. To further understand the mechanism underlying the cytotoxicity of 5-methoxy-1,4-naphthoquinone, studies involving DNA fragmentation, cell cycle analysis, phosphatidyl serine externalization, mitochondrial depolarization and activation of caspases 8 and 3/7 were performed in HL-60 cell line, using doxorubicin as a positive control. The results indicate that the cytotoxic 5-methoxy-1,4-naphthoquinone activates caspases 8 and 3/7 and thus induces apoptosis independent of mitochondria.

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