Synergistic effects of tamoxifen and cepharanthine for circumventing the multidrug resistance.
We examined the synergistic effects of tamoxifen (TAM) and cepharanthine (CEP) for doxorubicin (DOX) sensitivity using MTT assay. The augmentation of DOX sensitivity by TAM and CEP was significantly correlated with the P-glycoprotein expression. The cytotoxic effect of DOX with TAM and CEP was significantly higher than that of DOX alone, or DOX with TAM, and this synergistic effect was dominant in cell lines with high expression of P-glycoprotein. It was also examined that the intracellular concentration of DOX was increased in combined exposure of TAM and CEP, compared with the exposure of TAM, because TAM and CEP promoted the influx and inhibited the efflux of DOX. Thus, TAM and CEP might be able to circumvent DOX-resistance for treatment in cancer patients.
Second Department of Surgery, Wakayama Medical School, Japan.
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T
Hotta
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H
Tanimura
H
H
Yamaue
M
M
Iwahashi
M
M
Tani
T
T
Tsunoda
K
K
Noguchi
S
S
Mizobata
H
H
Terasawa
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002460:Cell Line; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology*; D052117:Benzodioxoles
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D004317:Doxorubicin; D013629:Tamoxifen; C006947:cepharanthine; D052117:Benzodioxoles