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 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 (IC(50) values of 0.03 and 0.08 microg/ml, respectively), whereas Dx was equally active in the two cell lines (IC(50) 0.12 microg/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 p21(waf1) expression. In MCF7 cells, treatment with L-Ann or Dx induced an increase in p53 expression with a consequent transactivation of p21(waf1) 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.
Orlandi
L
L
Dipartimento di Oncologia Sperimentale, Unita' Operativa # 10, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy.
Bertoli
G
G
Abolafio
G
G
Daidone
M G
MG
Zaffaroni
N
N
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin; C080315:annamycin