Interactions of iron-anthracycline complexes with living cells: a microspectrofluorometric study.
The interaction of iron-anthracycline complexes with tumor cells has been studied using microspectrofluorometry. The anthracyclines used were adriamycin, 4'-O-tetrahydropyranyladriamycin and daunorubicin. In every case, a 1:3 Fe(III)-anthracycline complex is formed. The three daunorubicin molecules that bind to one Fe(III) are not chemically modified through complexation with iron. In the case of the Fe(III)-adriamycin and Fe(III)-4'-O-tetrahydropyranyladriamycin complexes, about one of the three anthracycline molecules is chemically modified, yielding a highly lipophilic derivative, the 7,8-dehydro-9,10-desacetyladriamycin. The others molecules remain unchanged, i.e., highly hydrophilic in the case of adriamycin. These two species have a different fluorescent spectrum and can be identified inside the cell, using microspectrofluorometry. In the case of the Fe(III)-adriamycin complex, the lipophilic derivative is more rapidly internalized in the cell than the hydrophilic one. Diffusion into the plasmic membrane is the limiting step for the uptake of anthracycline by cells; this means that the plasmic membrane speeds up the dissociation of the Fe(III)-anthracycline complex.
Fiallo
M
M
Laboratoire de Physique et Chimie Biomoléculaires, Université Pierre et Marie Curie, Paris, France.
Laigle
A
A
Garnier-Suillerot
A
A
Amirand
C
C
Ballini
J P
JP
Chinsky
L
L
Duquesne
M
M
Jolles
B
B
Sureau
F
F
Turpin
P Y
PY
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D009942:Organometallic Compounds; C041415:doxorubicin-iron complex; D004317:Doxorubicin; C027260:pirarubicin; D007501:Iron; D003630:Daunorubicin