Anthracycline Efficacy in vitro: Cytotoxicity of Liposomal/Nonliposomal Daunorubicin and Doxorubicin for Multiple Tumor Cell Types

Abstract

Anthracyclines, including daunorubicin (DnR) and doxorubicin (DoX), have shown clinical chemotherapeutic utility, albeit in association with cumulative dose-associated cardiotoxicities. Despite structural similarity, however, DnR and DoX treatments have been directed toward leukemias and solid tumor types, respectively. Due to a paucity of in vitro data regarding differential use of DnR or DoX, we assessed the cytotoxicity of these compounds against solid and hematological tumor cell types. In addition, we examined liposomal formulations of DnR (L-DnR) and DoX (PEG-DoX), which, in contrast to DnR or DoX, demonstrate antineoplastic activity with reduced cardiotoxicity in vivo. Accordingly, cytotoxicity testing (with [methyl/-³H]thymidine incorporation) of DnR, DoX, L-DnR, and PEG-DoX on a range of different human tumor cell lines (e.g., breast, lung, ovarian, prostate, melanoma, lymphoma, and leukemia tumor cell types) was performed. Our data indicate comparable activity for DnR, DoX, or L-DnR in all tumor cell types examined [e.g., SK-BR-3 (breast adenocarcinoma) cells: IC₅₀ values = 5.9, 9.1, and 4.7 ng/mL for DnR, DoX, and L-DnR respectively]. In addition, several solid tumor cell types were more responsive to DnR than DoX [e.g., DU-145 (prostate carcinoma) cells: IC₅₀ values = 10.4 and 41.2 ng/mL for DnR and DoX, respectively; p >. 001]. Interestingly, PEG-DoX was substantively less effective for all tumor cells (IC₅₀ values were about 100-10,000 times greater for PEG-DoX than for DnR, DoX, or L-DnR; p >. 001, all cases). Reduced PEG-DoX activity in vitro may be related to polyethylene glycol (PEG) moieties present on the liposomal exterior of PEG-DoX, which are not present on L-DnR. Nonetheless, taken together, these data suggest that DnR and DoX demonstrate comparable efficacy in vitro and that specific liposomal encapsulation (L-DnR) does not mitigate DnR efficacy in vitro.