Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Campus do Porangabussu, Caixa Postal 3157, Fortaleza, Ceará, 60430-270, Brazil.
Chem Biol Interact. 2010 Mar 30;184(3):439-48. doi: 10.1016/j.cbi.2010.01.041. Epub 2010 Feb 4.
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.
对 9 种萘醌（NQ）的细胞毒性进行了测定，方法是在 72 小时孵育后，测定其对 HL-60（白血病）、MDA-MB-435（黑色素瘤）、SF-295（脑）和 HCT-8（结肠）等人类癌细胞系以及外周血单核细胞（PBMC）的抑制作用，后者作为正常细胞的代表。5-甲氧基-1,4-萘醌是最活跃的化合物，在 HL-60 中的 IC50 值范围为 0.31（1.7μM）至 SF-295 中的 0.88μg/mL（4.7μM），在 PBMC 中的 IC50 为 0.69μg/mL（3.7μM）。在胡桃醌的 2 位或 3 位引入溴取代基，无论取代基在萘醌部分的位置如何，IC50 值都会显著降低。然而，与胡桃醌甲醚相比，卤素取代降低了活性。为了进一步了解 5-甲氧基-1,4-萘醌细胞毒性的机制，用阿霉素作为阳性对照，在 HL-60 细胞系中进行了 DNA 片段化、细胞周期分析、磷脂酰丝氨酸外化、线粒体去极化和 caspase 8 和 3/7 激活等研究。结果表明，具有细胞毒性的 5-甲氧基-1,4-萘醌激活了 caspase 8 和 3/7，从而诱导了不依赖于线粒体的细胞凋亡。
