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This study was undertaken to examine the anticancer effects of the natural product rhein on human leukaemia cells. Material and methods: Cell viability was determined by MTT assay. Immunofluorescence staining, DAPI, AO/EB, and annexin V/PI staining were used for the detection of apoptosis. qRT-PCR analysis was used to examine protein expression. Western blot analysis was used to determine protein expression. Results: The results revealed that rhein caused a significant (p < 0.05) and dose-dependent decrease in the viability of AML-193 leukaemia cells. It was also revealed that rhein caused morphological changes such as cell rounding in rhein-treated AML-193 cells. The DAPI and AO/EB staining showed that rhein caused remarkable changes in the nuclear morphology of the AML-193 cells, characteristic of apoptosis. The percentage of apoptosis was found to be 3.12%, 14.80%, 30.31%, and 60.85% at the concentrations of 0, 3.5, 7, and 14 μM of rhein, respectively. The expression of Bax, cleaved caspase-3, 9, and cleaved PARP increased concentration dependently, while the expression of Bcl-2 decreased. The effects of rhein were also examined on 11 different miRs, and it was found that rhein specifically and significantly (p < 0.05) inhibited the expression of miR-27. Additionally, inhibition of miR-27 resulted in the decrease of AML-193 viability and upregulation of Cullin 5 (CUL5). Conclusions: Taken together, rhein triggers apoptosis in leukaemia cells and modulates the miR-27/CUL5 axis. As such, rhein may prove to be beneficial in the treatment of leukaemia.

Rhein regulates the proliferation and apoptosis of human leukaemia cells and its effects on the miR-27/CUL5 axis