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KMID : 0043320080310101355
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Archives of Pharmacal Research
2008 Volume.31 No. 10 p.1355 ~ p.1361
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Extensive Intracellular Accumulation of ID-6105, a Novel Anthracycline, in SK-OV-3 Ovarian Cancer Cells
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Jung Yeun-Bok
Lee Chong-Kil
Song Suk-Gil
Kim Tae-Yong
Lee Hong-Sub
Cho Byung-Suk
Choi Kyu-Seok
Shin Dae-Hwan
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Abstract
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We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, on weakly doxorubicin (Dox)-resistant SK-OV-3 ovarian cancer cells, and elucidated the relationship between its anticancer activity and accumulation in cells compared with those of Dox. Accumulation of ID-6105 in the cells was time- and concentration-dependent, a result of drug-induced cytotoxicity in the cells. SK-OV-3 cells were preloaded with ID-6105 or Dox for 12 h at concentrations ranging from 100 to 2000 nM and then incubated with drug-free medium for 0-48 h. Cell viability was measured using a proliferation-based assay (XTT assay). The inhibitory effects of ID-6105 on cell viability were more pronounced than those of Dox. The IC50 values of ID-6105 after 24- and 48-h incubation with drug-free medium were 1.58 and 0.084 μM, while those of Dox were 2 and 0.334 μM, respectively. To investigate the relationship between the intracellular levels and the cytotoxic effects of the drugs, we preloaded SKOV-3 cells with ID-6105 or Dox (100-2000 nM) for 12 h and then measured the intracellular levels of drugs by HPLC in drug-free medium for 0-48 h. After preloading the drugs, the intracellular concentrations of ID-6105 at time 0 were 1.3-, 1.8-, and 1.4-fold larger than those of Dox at initial concentrations of 500, 1000, and 2000 nM, respectively. The extent of ID-6105 accumulation in the cells was more pronounced than that of Dox. These findings suggest that ID-6105 effluxed less from the cells than Dox, resulting in its extensive cytotoxicity compared with that of Dox. These results show that accumulation of ID-6105 within tumor cells may be important for the inhibitory effects of this drug in cancer cells. ID-6105 has an antiproliferative effect on SK-OV-3 cells that is due to its cytotoxicity. This effect is more pronounced than that of Dox, and may be attributed to extensive accumulation of ID-6105 in the cells.
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KEYWORD
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ID-6105, Doxorubicin, Cytotoxicity, Accumulation, SK-OV-3 cells
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