Mechanisms of induction of apoptosis by anthraquinone anticancer drugs aclarubicin and mitoxantrone in comparison with doxorubicin: Relation to drug cytotoxicity and caspase-3 activation |
| |
Authors: | Email author" target="_blank">A?Koceva-Chy?aEmail author M?Jedrzejczak J?Skierski K?Kania Z?Jó?wiak |
| |
Institution: | (1) Department of Thermobiology, University of Łódź, Łódź, Poland;(2) Flow Cytometry Laboratory, National Institute of Public Health, Warsaw, Poland;(3) Department of Thermobiology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland |
| |
Abstract: | We examined molecular events and morphological features associated with apoptosis induced by anthraquinone anticancer drugs
aclarubicin, mitoxantrone and doxorubicin in two spontaneously immortalized cell lines (NIH 3T3 and B14) in relation to cytotoxicity
of these drugs. The investigated cells showed similar sensitivity to aclarubicin but different sensitivity to doxorubicin
and mitoxantrone: mitoxantrone was the most cytotoxic drug in both cell lines. All three drugs triggered both apoptosis and
necrosis but none of these processes was positively correlated with their cytotoxicity. Apoptosis was the prevalent form of
cell kill by aclarubicin, while doxorubicin and mitoxantrone induced mainly the necrotic mode of cell death. The extent and
the timing of apoptosis were strongly dependent on the cell line, the type of the drug and its dose, and were mediated by
caspase-3 activation. A significant increase in caspase-3 activity and the percentage of apoptotic cells, oligonucleosomal
DNA fragmentation, chromatin condensation and formation of apoptotic bodies was observed predominantly in B14 cells. NIH 3T3
cells showed lesser changes and a lack of DNA fragmentation. Aclarubicin was the fastest acting drug, inducing DNA fragmentation
12 h earlier than doxorubicin, and 24 h earlier than mitoxantrone. Caspase-3 inhibitor Ac-DEVD-CHO did not show any significant
effect on drug cytotoxicity and DNA nucleosomal fragmentation. |
| |
Keywords: | anthraquinones apoptosis caspases cytotoxicity immortalized cells necrosis |
本文献已被 PubMed SpringerLink 等数据库收录! |
|