Abstract
Liver cancer is associated with high mortality, particularly in patients infected with the hepatitis B virus. Treatment methods remain very limited. Here, we explored the effects of 17β-estradiol (E2) on apoptosis of various liver cell lines (LO2, HepG2, and HepG2.2.15 cells). Within a certain concentration range, 17β-estradiol induced oxidative stress and apoptosis of HepG2 cells, downregulated ERα-36 expression, and increased Akt and Foxo3a phosphorylation. p-Foxo3a became localized around the nucleus but did not enter the organelle. The levels of mRNAs encoding manganese superoxide dismutase (MnSOD) and catalase, to the promoters of which Foxo3a binds to trigger gene expression, were significantly reduced in HepG2 cells. 17β-estradiol had no obvious effects on LO2 or HepG2.2.15 cells. We speculate that 17β-estradiol may induce oxidative stress in HepG2 cells by increasing Foxo3a phosphorylation, thus promoting apoptosis. This may serve as a new treatment for hepatocellular carcinoma.
Highlights
Liver cancer is common and associated with high mortality (Mak et al, 2018); hepatocellular carcinoma (HCC) is the most common cancer type (Liu and Suo, 2020)
Sorafenib was the first such oral drug approved by the European Medicines Agency and Food and Drug Administration to treat primary liver cancer
HepG2, HepG2.2.15, and LO2 cells were treated with 17βestradiol (0.01 μg/ml to 25 μg/ml) for 24, 48, and 72 h (Figure 1A). 17β-estradiol at 0.01–0.5 μg/ml had no effect on LO2 cell proliferation but significantly inhibited proliferation at 5–25 μg/ml (p < 0.01)
Summary
Liver cancer is common and associated with high mortality (Mak et al, 2018); hepatocellular carcinoma (HCC) is the most common cancer type (Liu and Suo, 2020). The clinical effects on, and prognoses of, patients with advanced liver cancer are very poor; more effective therapies are needed (Bruix et al, 2019). Primary liver cancer occurrence and development is complex, involving multiple factors and several regulatory steps. Targeted therapy exploiting the abnormal signaling pathways of primary liver cancer are being intensively researched (Rossetto and De Re, 2019), as cancer occurrence and development remain poorly understood, and as the pathophysiological mechanism remains unclear, such therapies are not yet advanced. Sorafenib used as firstline treatment for HCC exhibits several side-effects, high-level drug-resistance development, and is associated with poor patient tolerance (Moawad et al, 2020)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
