Aclarubicin-induced apoptosis and necrosis in cells derived from human solid tumours.
In the present study, we investigated the response of A549 (non-small cell lung-cancer), HepG2 (human hepatoma) and MCF-7 (human breast adenocarcinoma) cell lines to treatment with aclarubicin (ACL). The aim of this research was to compare the ability of ACL to induce apoptosis or necrosis in solid tumours. The mode of cell death induced by ACL was evaluated by flow-cytometry and fluorescence microscopy. We show that the drug induced both apoptosis and necrosis in the cells. Apoptotic cell death was associated with morphological changes, DNA fragmentation, changes in activity of poly(ADP-ribose)polymerase (PARP) and drug-mediated activation of caspase-3 and caspase-8. The occurrence of all these events was time-dependent. The extent of apoptosis was also dependent on the kind of cell line, the sensitivity to ACL and the intracellular drug content. This study demonstrates that the cells most sensitive to ACL, A549, accumulated a significantly higher level of the drug and were also more susceptible to apoptosis than the other cells. In contrast, the relatively less sensitive HepG2 and MCF-7 cell lines appeared more resistant to apoptosis induction. On the basis of these results, it seems that aclarubicin is able to induce apoptosis in human solid tumours.
Rogalska
Aneta
A
Department of Thermobiology, University of Lodz, Banacha 12/16 st., 90-237 Lodz, Poland. zychan@biol.uni.lodz.pl
Szwed
Marzena
M
Jóźwiak
Zofia
Z
D015250:Aclarubicin / Q000378:metabolism / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020287:In Situ Nick-End Labeling; D009336:Necrosis / Q000139:chemically induced*; D011065:Poly(ADP-ribose) Polymerases; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D015250:Aclarubicin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8