Some insights into the cellular responses against doxorubicin and actinomycin D

ABSTRACT

Cellular responses to anti-cancer agents are an important factor in recognizing mechanisms of resistance and in identifying new treatment biomarkers. In this study, we have compared the effect of actinomycin D and doxorubicin on selected genes in the transcription and ubiquitin pathways. The human promyelocytic leukemia cells [HL60] was used as a model system and the chosen genes were POL2A and ELL2 [from transcription machinery] and UBE2DE and CDC [from ubiquitin pathway]. The responses of the four targeted genes suggested a degree of biological resistance amongst just those functions that might be expected to be damaged by the drug action. It is as if the cells are trying to upregulate these functions to offset drug inhibition. For example, doxorubicin up-regulated ubiquitinrelated genes suggesting an attempt to remove the trapped cleavable complex by an ubiquitin-dependent mechanism, while actinomycin up-regulated the transcription machinery genes suggesting an attempt to overcome the longed lived complexes that are formed by the actinomycin D on the DNA