Purpose: To study the anticancer potential of a plant-derived coumarin, Nodakenetin, against acute lymphocytic leukemia HL-60 cells.
Methods: The proliferation rate of the leukemia cells was checked by CCK-8 assay. Apoptotic cell death was studied by acridine orange (AO)/ethidium bromide (EB) staining. Cell cycle analysis was performed by flow cytometery. Cell migration and invasion were checked by transwell assay. Protein expression were determined by immuno blotting. Xenografted mice models were used for in vivo evaluation of Nodakenetin.
Results: Nodakenetin could significantly inhibit the proliferation of the all the leukemia cells. The anticancer activity of Nodakenetin against the HL-60 cells was found to be due to G2/M cell cycle arrest and induction of apoptosis. Nodakenetin prompted mitochondrial apoptosis which was also associated with alteration in the apoptosis-related protein expression (Bax and Bcl-2). It was also observed that Nodakenetin could inhibit the migration and invasion of the leukemia cells in a concentration-dependent manner. The effects of the Nodakenetin were also investigated in vivo in xenografted mice models and it was found that this molecule could inhibit the growth of xenografted tumors.
Conclusions: These results indicate Nodakenetin significantly inhibits the growth of leukemia cells in vitro and in vivo and may be a valuable molecule in the management of leukemia, and as such needs further in depth investigations.