Dehydrocostus lactone promotes ferroptosis by regulating the HMOX1/CDK1 axis during liver cancer treatment

Dehydrocostus lactone (Dehy) is the main component of Saussurea lappa and has been shown to have anti-inflammatory and anti-cancer properties. This study aimed to explore the specific mechanism of action of Dehy in liver cancer. Dehy can effectively promote liver cancer cell apoptosis, and inhibit proliferation, invasion and migration, in a dose-dependent manner, using CCK-8 assay, flow cytometry, transwell invasion and wound healing assays. Identification of 2202 and 5549 differential expression genes with transcriptome sequencing analysis, respectively, at the gene expression level and transcript level, and discovered that they are related to ferroptosis. Then, discovered that only HMOX1 is the ferroptosis-related key gene using network pharmacology analysis. Dehy promoted liver cancer cell ferroptosis by up-regulating HMOX1. Moreover, HMOX1 negative regulation targets the gene CDK1. Dehy decreased the expression of CDK1 by up-regulating the expression of HMOX1, which promoted liver cancer cell ferroptosis. Subsequently, Dehy played an anti-tumor role and promoted the ferroptosis effect in vivo xenograft mouse models. Collectively, our findings demonstrate that Dehy can effectively promote liver cell ferroptosis in vitro and in vivo. Dehy exerts an anti-cancer function in liver cancer by regulating the HMOX1/CDK1 axis.