Hirsutanonol Inhibits the Progression of Hepatocellular Carcinoma by Promoting the Expression of CNDP1

Hepatocellular Carcinoma (HCC) is a malignant tumor originating from hepatocytes. Hirsutanonol is a secondary metabolite derived from the bark of Alnus japonica that has multiple biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, its role and underlying mechanism in hepatocellular carcinoma remain unclear. This study aimed to explore the effects of Hirsutanonol on HCC cells and its related molecular mechanism.

First, EdU staining, Annexin V-FITC staining, cell scratch assays, Transwell chamber assays, and other experiments were performed to determine the effects of different concentrations of hirsutanonol on the proliferation, apoptosis, migration, and invasion of Huh7 cells. Furthermore, a mouse subcutaneous xenograft model was established to verify the inhibitory effect of Hirsutanonol on the in vivo growth of Huh7 cells. Molecular docking, CETSA, and Western blotting were subsequently performed to explore the binding interaction between Hirsutanonol and CNDP1 as well as the regulatory effect of Hirsutanonol on CNDP1 expression. Finally, rescue experiments were performed to investigate the influence of CNDP1 silencing on the tumor-suppressive function of hirsu-tanonol.

Hirsutanonol effectively inhibited the malignant biological behaviors of Huh7 cells, including proliferation, migration, and invasion, while promoting Huh7 apoptosis. Moreover, it suppressed the in vivo growth of Huh7 cells in mice. Mechanistic studies further confirmed that hirsutanonol can bind to CNDP1 and upregulate its expression, thereby inhibiting activation of the PI3K/AKT/mTOR signaling pathway. Moreover, silencing CNDP1 expression significantly reversed the inhibitory effects of Hirsutanonol on the proliferation, migration, and invasion of Huh7 cells, as well as its pro-apoptotic effect on Huh7 cells.

Hirsutanonol can effectively inhibit the proliferation, migration, and invasion of Huh7 cells, as well as their tumorigenicity in the subcutaneous layer of mice. Targeted binding to CNDP1 and promoting its expression may be important mechanisms through which Hirsutanonol exerts its anticancer function.

Hirsutanonol can upregulate CNDP1 expression in a targeted manner and exhibit anticancer effects in HCC. These findings not only expand the biological functions of Hirsutanonol but also provide a theoretical basis for the pharmacological treatment of HCC in the future, thereby indicating that Hirsutanonol has a certain scientific significance and potential clinical application value.