Mechanisms of induction of apoptosis by anthraquinone anticancer drugs aclarubicin and mitoxantrone in comparison with doxorubicin: Relation to drug cytotoxicity and caspase-3 activation

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.

Cytotoxic and antimigratory effects of Cratoxy formosum extract against HepG2 liver cancer cells

“…Various studies have screened for compounds that trigger apoptosis by measuring caspase activity and mitochondrial membrane potential (28). Caspase enzymes are proteases that are used to determine whether apoptosis is being triggered via the intrinsic or extrinsic pathway (29).…”

Nanoparticles with Therapeutic Properties Generate Various Response of Human Peripheral Blood Mononuclear Cells

“…To 100 l of cell suspension, 1 l of Hoechst 33258 (0.13 mM) and 1 l PI (0.23 mM) were added and the cells were incubated at room temperature for 10 min in the dark. The cells were classified on the basis of their morphological and staining characteristics as: live (pale-blue fluorescence), apoptotic cells (intensive bright-blue and blue-violet fluorescence), and necrotic (red fluorescence) 8. At least 300 cells were counted on each slide and each experiment was done in triplicate.…”

Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone

“…Aclarubicin, although considerably less toxic than mitoxantrone, displays higher pro-apoptotic activity and induces apoptosis after shorter time of exposure. At the same time B14 cells are more prone to the induction of apoptosis by the investigated drugs than NIH 3T3 cells (Koceva-Chy1a et al, 2005). Thus, we conclude that different response of both cell lines to apoptotic stimuli might also contribute to their different response to LPL after cell sensitizing with aclarubicin.…”