Effects of liposome-entrapped annamycin in human breast cancer cells: Interference with cell cycle progression and induction of apoptosis

Linda Orlandi, Gloria Bertoli, Gabriella Abolafio, Maria Grazia Daidone, Nadia Zaffaroni

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of liposome-encapsulated annamycin (L-Ann) were investigated in two human breast cancer cell lines, MCF7 and MDA-MB-435. For comparative purposes, doxorubicin (Dx) was used throughout the study. A 4-hour treatment with L-Ann was significantly more active in MDA-MB-435 than in MCF7 cells (IC50 values of 0.03 and 0.08 μg/ml, respectively), whereas Dx was equally active in the two cell lines (IC50 0.12 μg/ml). L-Ann induced an accumulation of cells in G2M phases which was dose-dependent in MDA-MB-435 but not in MCF7 cells. Dx also caused a dose-dependent increase of G2M cell fraction in MDA-MB-435 cells, whereas a G2M cell accumulation was observed only after treatment with the highest Dx concentration in MCF7 cells. G2M phase cell accumulations induced in MCF7 cells by L-Ann or Dx were accompanied by a decrease in cdc2 kinase activity and in cyclin B1 and cdc2 expression. Conversely, in MDA-MB-435 cells exposed to L-Ann or Dx, cdc2 kinase activity, cyclin B1 and cdc2 expression increased in parallel to the increase in the number of cells accumulated in the G2M phase. L-Ann and Dx induced apoptosis in MDA-MB-435 but not in MCF7 cells. In MDA-MB-435 cells exposed to L-Ann or Dx, no change was observed in the expression of bax, but there was a p53-independent increase in p21waf1 expression. In MCF7 cells, treatment with L-Ann or Dx induced an increase in p53 expression with a consequent transactivation of p21waf1 and bax. Our results indicate that L-Ann is more cytotoxic than Dx in breast cancer cells and is able to induce apoptosis through p53-independent mechanisms.

Original languageEnglish
Pages (from-to)9-22
Number of pages14
JournalJournal of Cellular Biochemistry
Volume81
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Anthracyclines
  • cdc2 kinase
  • Cell proliferation
  • Flow cytometry
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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