Influence of cepharanthin on the intracellular accumulation of adriamycin in normal liver cells and spleen cells of mice in vitro and in vivo.
Cepharanthin enhances the cytotoxicity of adriamycin by inhibiting its efflux incorporated into cancer cells. Therefore, it may also enhance accumulation of adriamycin, and then enhance toxicity by adriamycin in normal cells as well as in cancer cells. In this study, we first examined influence of cepharanthin on the accumulation of adriamycin in normal liver cells or spleen cells in vitro and in vivo. Cepharanthin lowered the accumulation of adriamycin in liver cells, in both in vitro and in vivo. In spleen cells, it enhanced adriamycin accumulation slightly in vitro, but did not affect that in vivo. Further, cepharanthin lowered the amount of adriamycin in plasma. This suggests that decreased levels of adriamycin in plasma may be one of factors in the decrease of adriamycin accumulation in liver cells. On the other hand, cepharanthin enhanced the NK 2280 accumulation used for an indicator of cell membrane potential for 60-100 minutes in liver cells, but did not change that in spleen cells. These suggest that the cell membrane potential may not affect the adriamycin accumulation in both cells since adriamycin accumulation increases with increasing accumulation of NK-2280. Moreover, no change in adriamycin efflux of liver cells was demonstrated by the treatment of cepharanthin. This indicates that the decrease in adriamycin accumulation in liver cells may not be due to the inhibition of adriamycin efflux. In conclusion, cepharanthin enhances adriamycin accumulation in cancer cells, but lowers its accumulation in normal liver cells and does not affect that in spleen cells. Therefore, cepharanthin may be useful in cancer chemotherapy.
Nishikawa
K
K
Department of Radiology, Okayama University Medical School, Japan.
Asaumi
J
J
Kawasaki
S
S
Kuroda
M
M
Takeda
Y
Y
Hiraki
Y
Y
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D001692:Biological Transport / Q000187:drug effects; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D013154:Spleen / Q000378:metabolism*; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D002232:Carbocyanines; D004317:Doxorubicin; D005456:Fluorescent Dyes; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; C006947:cepharanthine; D052117:Benzodioxoles