Synergistic anti-tumor effects of mitomycin C and bile salts against L1210 cells.
The effects of various adjuvants on the cytotoxicity of mitomycin C (MMC) were studied in L1210 mouse leukemia cells. Adjuvants examined in this study were sodium glycocholate (Na-GC), sodium deoxycholate (Na-DC), O-n-dodecyl-beta-D-maltopyranoside (LM), and sodium salicylate. Among various additives, bile salts such as Na-GC and Na-DC were the most effective for increasing the cytotoxicity of MMC against L1210 cells. A dose-dependent increase in cytotoxic effect of MMC was observed in the presence of these bile salts. To elucidate a possible mechanism for enhancing the cytotoxic effect of MMC by the bile salts, the cellular uptake of MMC with or without Na-GC was examined using L1210 cells. The cellular concentration of MMC was determined by a reversed-phase HPLC. When Na-GC was coadministered with MMC, the uptake of MMC into L1210 cells was significantly enhanced as compared with MMC alone. Furthermore, the membrane fluidity of L1210 cells, as determined by fluorescence polarization, was increased in the presence of Na-GC. These results suggested that the enhancement of cytotoxicity of MMC by the addition of Na-GC could be attributed to the increasing cellular uptake of MMC due to the increasing membrane fluidity of L1210 cells.
Tamura
T
T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Fujita
T
T
Itoh
Y
Y
Sugimoto
S
S
Yamada
H
H
Murakami
M
M
Yamamoto
A
A
Muranishi
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D004357:Drug Synergism; D005456:Fluorescent Dyes; D006000:Glycocholic Acid / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy*; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D004161:Diphenylhexatriene; D016685:Mitomycin; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D006000:Glycocholic Acid