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논문 기본 정보

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저자정보
Shin, Dae-Hwan (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University) Choi, Kyu-Seok (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University) Park, Sang-Ae (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University) Cho, Byung-Suk (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University) Lee, Hong-Sub (Research Laboratories, ILDONG Pharmaceutical Co., Ltd.) Ryu, Jung-Su (Research Laboratories, ILDONG Pharmaceutical Co., Ltd.) Kim, Tae-Yong (Research Laboratories, ILDONG Pharmaceutical Co., Ltd.) Lee, Chong-Kil (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University) Song, Suk-Gil (National Research Laboratory [NRL] of PK/PD, CBITRC, Biotechnology Research Institute, College of Pharmacy, Chungbuk National Universi) Chung, Youn-Bok
저널정보
대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제31권 제10호
발행연도
2008.1
수록면
1,355 - 1,361 (7page)

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We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6l05), 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-6l05 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-6l05 on cell viability were more pronounced than those of Dox. The $IC_{50}$ values of ID-6105 after 24- and 48-h incubation with drug-free medium were 1.58 and $0.084{\mu}M$, while those of Dox were 2 and $0.334{\mu}M$, respectively. To investigate the relationship between the intracellular levels and the cytotoxic effects of the drugs, we preloaded SK-OV-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 l,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.
#ID-6105 #Doxorubicin #Cytotoxicity #Accumulation #SK-OV-3 cells

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