A comparative study of the effects of anthracycline derivatives on a human adenocarcinoma cell line (LoVo) grown as a monolayer and as spheroids.
The cytotoxicity of doxorubicin (DX), 4'-O-methyl-DX (MET-DX), 4'-deoxy DX (DEO-DX), 4'-deoxy-4'-iodo-DX (IODO-DX), daunorubicin (DNR)and 4-demethoxy-DNR (DM-DNR) on LoVo cells cultured as a monolayer (in exponential and stationary phases of growth) and as spheroids, are evaluated following 1-h exposure to the drugs. All compounds were more cytotoxic than DX in both systems. A comparison of the ID50 values for cell survival of monolayer cells and of the inhibition of relative growth of individual spheroids indicated that MET-DX and DNR, like DX, were less cytotoxic on spheroids than on monolayer cells in both growth conditions; DEO-DX, IODO-DX and DM-DNR showed an activity on spheroids that was intermediate between that observed on monolayer cells in exponential and stationary phases of growth. This observation indicated that the different pattern of activity of these anthracyclines on a spheroids system is not only related to the presence of cells at different cell cycle phases, but presumably also depends on factors related to the 3-dimensional structure of spheroid cells. Indeed DEO-DX, IODO-DX and DM-DNR, more lipophilic than the other compounds, might penetrate more deeply into spheroids, thus improving the cytotoxic response in this experimental system.
Soranzo
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C
Division of Experimental Oncology B, Istituto Nazionale per to Studio e la Cura dei Tumori, Milano, Italy.
Ingrosso
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A
D000230:Adenocarcinoma / Q000473:pathology; D002453:Cell Cycle; D003110:Colonic Neoplasms / Q000473:pathology; D046508:Culture Techniques / Q000379:methods; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004317:Doxorubicin; D003630:Daunorubicin