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

The effects of liposome-encapsulated annamycin (L-Ann) were investigated in two human breast cancer cell lines, MCF7 and MDA-MB-435. For comparative p urposes, 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 (ICS, values of 0.03 and 0.08 mug/ml, respectively), whereas Dx was equally active in the two cell lines (IC50 0.12 mug/ml). L-Ann induced an accumula tion of cells in G(2)M phases which was dose-dependent in MDA-MB-435 but no t in MCF7 cells. Dx also caused a dose-dependent increase of G(2)M cell fra ction in MDA-MB-435 cells, whereas a G2M cell accumulation was observed onl y after treatment with the highest Dx concentration in MCF7 cells. G2M phas e 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 activi ty, cyclin B1 and cdc2 expression increased in parallel to the increase in the number of cells accumulated in the G(2)M phase. L-Ann and Dx induced ap optosis 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 wa s a p53-independent increase in p21(waf1) expression. In MCF7 cells, treatm ent with L-Ann or Dr induced an increase in p53 expression with a consequen t transactivation of p21(waf1) and bax. Our results indicate that L-Ann is more cytotoxic than Dr in breast cancer cells and is able to induce apoptos is through p53-independent mechanisms. (C) 2001 Wiley-Liss, Inc.