Image1_Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells.pdf
Acute myeloid leukemia (AML) is one of the malignant hematological cancers with high mortality. Finding a more effective and readily available treatment is of the utmost importance. Here, we aimed to identify the anti-leukemia effect of a natural small molecule compound honokiol on a panel of AML cell lines, including THP-1, U-937, and SKM-1, and explored honokiol’s potential biological pathways and mechanisms. The results showed that honokiol decreased the viability of the targeted AML cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. Subsequent studies verified that HMOX1 was a critical target in honokiol-induced ferroptosis. These results reveal that honokiol is an effective anti-leukemia agent in AML cell lines and may be a potential ferroptosis activator in AML.
History
References
- https://doi.org//10.2174/156652412803833508
- https://doi.org//10.1016/j.phrs.2019.04.004
- https://doi.org//10.1016/j.canlet.2017.12.025
- https://doi.org//10.1007/s11864-019-0612-y
- https://doi.org//10.1016/j.bcp.2008.06.012
- https://doi.org//10.1016/j.cell.2012.03.042
- https://doi.org//10.3390/v7092852
- https://doi.org//10.1182/blood.2020005524
- https://doi.org//10.1182/blood-2005-08-3181
- https://doi.org//10.1172/JCI99032
- https://doi.org//10.1038/s41418-021-00768-1
- https://doi.org//10.1172/JCI141529
- https://doi.org//10.1007/s13238-020-00789-5
- https://doi.org//10.1158/1078-0432.CCR-10-0333
- https://doi.org//10.1002/jcb.24967
- https://doi.org//10.1111/jcmm.15148
- https://doi.org//10.1155/2020/3469840
- https://doi.org//10.1016/j.ejphar.2008.06.026
- https://doi.org//10.1056/NEJMoa1300874
- https://doi.org//10.1016/j.clml.2021.06.002
- https://doi.org//10.1038/s41375-019-0390-3
- https://doi.org//10.1038/s41420-020-00315-w
- https://doi.org//10.1080/10408398.2018.1509201
- https://doi.org//10.3390/biom11060907
- https://doi.org//10.3390/cancers12010048
- https://doi.org//10.1002/jcp.22954
- https://doi.org//10.1016/s0891-5849%2899%2900223-3
- https://doi.org//10.1016/j.blre.2019.04.005
- https://doi.org//10.3322/caac.21654
- https://doi.org//10.1159/000486228
- https://doi.org//10.1080/10428194.2019.1613540
- https://doi.org//10.1016/j.cell.2017.09.021
- https://doi.org//10.3390/ijms19113325
- https://doi.org//10.1038/s41422-020-00441-1
- https://doi.org//10.1016/j.redox.2021.101971
- https://doi.org//10.1182/blood.2020008551
- https://doi.org//10.2147/CMAR.S187597
- https://doi.org//10.1080/10428194.2017.1390229
- https://doi.org//10.1111/tra.12611