[Combination of a biscoclaurine alkaloid, cepharanthine, and anticancer agents: effects and mechanism in human gastric and pancreatic carcinoma cell lines].
A biscoclaurine alkaloid, cepharanthine (CE) potentiated antitumor activity of doxorubicin (ADM) against human carcinoma cell lines, K 562 (myelogenous leukemia), PH 101 (pancreas cancer) and SH 101 (gastric cancer). The effect of CE was irreversible and ADM activity was potentiated only in the presence of CE. While, CE could not augment anticancer activities of mitomycin C (MMC) or 5-fluorouracil (5-FU). We also found an increase of cellular plasma membrane potential in the presence of CE. In physiological condition, ADM was charged positively, while MMC or 5-FU was neutrally charged compound. Thus, we suggest that CE can potentiate the activity of positively charged anticancer drugs by increasing plasma membrane potential. Since electronegative plasma membrane potential exerts a net driving force which attracts and retains positively charged compound, it may be accompanied with an increase of drug accumulation.
Nishiyama
M
M
Dept. of Surgery, Hiroshima University, Japan.
Aogi
K
K
Saeki
S
S
Hirabayashi
N
N
Toge
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D052117:Benzodioxoles
D000470:Alkaloids; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D004317:Doxorubicin; D005472:Fluorouracil; D016685:Mitomycin; C006947:cepharanthine; D052117:Benzodioxoles