Time- and concentration-dependent apoptosis and necrosis induced by free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells

Marina Demoy, Tamara Minko, Pavla Kopečková, Jindřich Kopeček

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

A2780 sensitive and A2780/AD doxorubicin (DOX) resistant human ovarian carcinoma cells were exposed to different concentrations (0.25, 0.5, 1, 5 and 10xIC50) of free and HPMA copolymer-bound DOX for 12, 24, 36, 48, 60 and 72 h. Apoptosis and necrosis were evaluated using the FITC-conjugated annexin V and propidium iodide staining. The data obtained showed that the induction of apoptosis and necrosis by both free DOX and HPMA copolymer-bound DOX were time- and concentration-dependent. The data also showed significant differences between the drugs. It was found that: (i) under the action of HPMA copolymer-bound doxorubicin the alterations in the plasma membrane permeability preceded disturbances in cellular metabolism; (ii) HPMA copolymer-bound doxorubicin kills the cells mainly by necrosis; (iii) HPMA copolymer-bound doxorubicin is a more effective anticancer drug than free doxorubicin. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)185-196
Number of pages12
JournalJournal of Controlled Release
Volume69
Issue number1
DOIs
StatePublished - Oct 3 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Apoptosis
  • Doxorubicin
  • HPMA copolymer
  • Necrosis
  • Ovarian carcinoma

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