Aloe-emodin's cytotoxicity against CCRF-CEM cells: NF-κB as a major player induces apoptosis

NF-κB family as being significant in inflammation and immunity also has a notable role in cancer initiation, progression and inhibition of programmed cell death [1 – 3], which indicates it's a crucial target for cancer. A main anthraquinone aglycone of Rumex and other genera (e.g. Aloe, Rheum and Rhamnus) aloe-emodin has cytotoxic effect against CCRF-CEM leukemia cells with the IC₅₀ value of 11.95µM. In the present study, we focused on the background mechanisms behind its cytotoxicity on the basis of pharmacogenomic approach. Therefore we performed microarray-based mRNA profiling which was validated by qPCR analysis. According to the Ingenuity Pathway Analysis of microarray data, we observed that NF-κB and the target genes of whom were downregulated causing apoptosis by aloe-emodin. We additionally conducted gene promoter binding motif analysis. NF-κB binding motifs were screened 75 kb upstream of the transcription start site of the genes of interest. To test aloe-emodin real act on NF-κB, we carried out NF-κB reporter assay and observed NF-κB downregulation by aloe-emodin in dose dependent manner which was upward of 50% with the treatment of 75µM or 100µM aloe-emodin. Inhibition of NF-κB was further proven by docking analysis. We specificied NF-κB as one of the major player determining the cytotocity of aloe-emodin against CCRF-CEM cells in addition to other cellular and molecular factors determined in our previous studies.

This study was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) 2214-A scholarship.

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