M. Demoy et al., Time- and concentration-dependent apoptosis and necrosis induced by free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells, J CONTR REL, 69(1), 2000, pp. 185-196
A2780 sensitive and A2780/AD doxorubicin (DOX) resistant human ovarian carc
inoma cells were exposed to different concentrations (0.25, 0.5, 1, 5 and 1
0XIC(50)) of free and HPMA copolymer-bound DOX for 12, 24, 36, 48, 60 and 7
2 h. Apoptosis and necrosis were evaluated using the FITC-conjugated annexi
n V and propidium iodide staining. The data obtained showed that the induct
ion of apoptosis and necrosis by both free DOX and HPMA copolymer-bound DOX
were time- and concentration-dependent. The data also showed significant d
ifferences between the drugs. It was found that: (i) under the action of HP
MA copolymer-bound doxorubicin the alterations in the plasma membrane perme
ability preceded disturbances in cellular metabolism; (ii) HPMA copolymer-b
ound doxorubicin kills the cells mainly by necrosis; (iii) HPMA copolymer-b
ound doxorubicin is a more effective anticancer drug than free doxorubicin.
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