In vivo augmentation of the intratumoral concentration of 5-fluorouracil by cepharanthine--a biscoclaurine alkaloid.
We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanaka
N
N
First Department of Surgery, Okayama University Medical School, Japan.
Kataoka
K
K
Muro
M
M
Kojima
K
K
Horiki
S
S
Ono
M
M
Moreira
L F
LF
Naomoto
Y
Y
Orita
K
K
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D044182:Benzylisoquinolines; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004357:Drug Synergism; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D052117:Benzodioxoles
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D005472:Fluorouracil; C006947:cepharanthine; D052117:Benzodioxoles