Hydrangea serrata extract exerts tumor inhibitory activity against hepatocellular carcinoma HepG2 cells via inducing p27/CDK2-mediated cell cycle arrest and apoptosis

Objective: To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms. Methods: The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays. Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis. Results: Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids. The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression, leading to cell cycle arrest. Moreover, increased BAX/Bcl-2 ratio as well as caspase-9 and - 3 were observed after treatment with Hydrangea serrata extract, indicating the induction of tumor cell apoptosis. Conclusions: Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis, thereby inhibiting tumor growth. Keywords: Hydrangea serrata, Hepatocellular carcinoma, Liver cancer, Anticancer, Cell cycle arrest, Apoptosis