[Assay of flow cytometry for the effect of cepharanthine on resistance to doxorubicin].
The biochemical activity of cepharanthine and the possible mechanism by which it reverses the resistance to doxorubicin in P388 leukemia cells were examined in vitro. The microfluorometric analysis of the cellular level of doxorubicin in drug-resistant cells showed that cepharanthine markedly enhanced the sensitivity of doxorubicin against resistant cells in the cellular level. Cepharanthine also enhanced the inhibitory effect of doxorubicin on the incorporation of thymidine into DNA in resistant cells. The analysis of DNA histogram obtained by flow cytometry showed that doxorubicin exerted its growth-inhibitory effect by blocking the cell cycle at the G2 phase in P388 cells. At higher concentrations, doxorubicin prolonged the S phase and inhibited cell cycle progression to the G2/M phase in cells. The treatment with cepharanthine potentiated these blocking effects induced by doxorubicin in cells. It seems that the modifications of the biological effect of doxorubicin by cepharanthine are due to the change of their ability to induce DNA damage in cells.
Kisara
S
S
Dept. Pharmacol. Toxicol., Tohoku College of Pharmacy, Sendai, Japan.
Hayashi
A
A
Maekawa
I
I
Furusawa
S
S
Takayanagi
Y
Y
Sasaki
K
K
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D007941:Leukemia P388 / Q000378:metabolism / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D004273:DNA, Neoplasm; D004317:Doxorubicin; D013936:Thymidine; C006947:cepharanthine; D052117:Benzodioxoles