Purpose: Esculetin is an important bioactive coumarin with amazing potential to suppress the growth of cancer cells. The present study was designed to investigate the anticancer effects of esculetin against the human leukemia HL-60 cells.
Methods: CCK-8 assay was used to assess cell viability. DAPI and annexin V/propidium iodide (PI) staining was performed to investigate the induction of apoptosis. Autophagy was detected by electron microscopic analysis. Flow cytometry was used for cell cycle analysis and Western blotting was used to estimate protein expression.
Results: Esculetin suppressed the proliferation of HL-60 cells dose-dependently. The IC50 of esculetin against HL-60 cells was observed to be 20 µM. The anticancer effects of esculetin against HL-60 cells occurred though different mechanisms. Esculetin induced apoptosis and autophagy in leukemia cells, which were accompanied by alteration in the expression of apoptosis as well as autophagy-related proteins. Esculetin also triggered G0/G1 cell cycle arrest in HL-60 cells, which was also accompanied by suppression of Cyclin D1 and D3. Esculetin could also block the Raf/MEK/ERK signalling pathway in leukemia cells in a concentration-dependent manner.
Conclusion: These results indicate that esculetin inhibits the growth of leukemia cells and hence may prove beneficial for treating leukemia.