Some Insights into the Cellular Responses Against Doxorubicin and Actinomycin D

Malek Zihlif, Hamza Beano, Mohammad Barouqa, Sameer Shwaiki, Randa Naffa

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 up-regulate these functions to offset drug inhibition. For example, doxorubicin up-regulated ubiquitin-related 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.

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