AUTHOR=Lai Xingrong , Sun Yanhua , Zhang Xuedi , Wang Dan , Wang Jialing , Wang Haihua , Zhao Yao , Liu Xinling , Xu Xin , Song Haoran , Ping Wenjia , Sun Yanli , Hu Zhenbo TITLE=Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.897791 DOI=10.3389/fphar.2022.897791 ISSN=1663-9812 ABSTRACT=

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.