Abstract
Relevant researches have recognized the vital role of inducing ferroptosis in the treatment of tumor. The latest findings indicate that PEBP1/15-LO can play an essential role in the process of cell death. However, its role in regulating ferroptosis in hepatocellular carcinoma (simplified by HCC) remains unclear. The previous research of our team has proved that DHA can induce ferroptosis of hepatic stellate cells. In this study, we found that DHA could also induce ferroptosis in HCC cells. Interestingly, DHA induced ferroptosis by promoting the formation of PEBP1/15-LO and promoting cell membrane lipid peroxidation. In addition, we also found that DHA had no obvious regulatory effect on 15-LO, but it could promote PEBP1 protein expression. Importantly, we discovered the upregulation of PEBP1 induced by DHA was related to the inhibition of its ubiquitination degradation. In vivo experiments have also obtained consistent results that DHA can inhibit tumor growth and affect the expression of ferroptosis markers in tumor tissues, which would be partially offset by interference with PEBP1.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with an extensive global influence
To clarify the effect of DHA in the development of HCC cells, HepG2 and Huh-7 cells were intervened with gradient DHA (0-100 μM) for 24 h, respectively, and cell proliferation was detected by MTT assay
ROS fluorescence probe was used to test the changes of ROS level in HCC cells after DHA treatment, and the results showed that the fluorescence intensity increased with the increase of DHA concentration (Figure 2(i)), indicating that DHA could induce the accumulation of ROS in HCC cells
Summary
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with an extensive global influence. HCC is found usually in the middle and advanced stage and has been unable to carry out effective surgical treatment. New and effective treatment regimens are urgently needed. The primary drugs used in tumor treatment are chemical synthesis drugs, which are extensively used but all have a number of serious side effects [2]. Traditional Chinese medicine effective component can target and regulate the expression of some proteins and genes of cell function, which makes the traditional Chinese medicine monomer compounds in the treatment of HCC play a more and more important role. It is important to find effective traditional Chinese medicine monomers for the prevention and treatment of liver cancer
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