Cepharanthin, a multidrug resistant modifier, is a substrate for P- glycoprotein

M. Hirai, K. Tanaka, T. Shimizu, Y. Tanigawara, M. Yasuhara, R. Hori, Y. Kakehi, O. Yoshida, K. Ueda, T. Komano, K. I. Inui

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


P-glycoprotein modulators are respected to be multidrug resistance reversing agents in cancer chemotherapy. Some calcium channel blockers, calmodulin inhibitors or immunosuppressive agents have been used in clinical studies, although the dose of these drugs required to test in vitro experimental data might cause potent pharmacological effects which are not desirable in patients. By using LLC-GA5-COL150 cells that express P- glycoprotein specifically on the apical membranes, we examined the transport of anticancer drugs mediated by P-glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the transport of vinblastine and daunorubicin, both commonly used anticancer agents. The 50% inhibitory concentration of cepharanthin on daunorubicin transport was 2.06 μM. Combined inhibitory effects on daunorubicin transport were observed when cepharanthin was used together with cyclosporin A, a potent immunosuppressive agent and P- glycoprotein modulator. Cepharanthin itself was transported by P- glycoprotein. Transcellular transport of cepharanthin across LLC-GA5-COL150 cell monolayers was saturable when its concentration was under 5 μM, and the transport was inhibited by P-glycoprotein modulators. These results indicate that cepharanthin can reverse multidrug resistance, and proper combination with other P-glycoprotein modulators could potentiate its inhibitory effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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