Hepatoblastoma is the most common primary liver tumor for children aged <5 years old. 20(S)‑Protopanaxadiol (PPD) is a ginsenoside extracted from Pananx quinquefolium L., which inhibits tumor growth in several cancer cell lines. The purpose of the present study was to assess the anticancer activities of 20(S)‑PPD in human hepatoblastoma HepG2 cells. The cytotoxicity of 20(S)‑PPD on HepG2 cells was evaluated using an MTT assay. Apoptosis was detected using DAPI staining and flow cytometry. The expression of apoptosis‑associated proteins was identified by western blotting. The results demonstrated that 20(S)‑PPD inhibited the viability of HepG2 cell in a dose and time‑dependent manner. The IC50 values were 81.35, 73.5, 48.79 µM at 24, 48 and 72 h, respectively. Topical morphological changes of apoptotic body formation following 20(S)‑PPD treatment were detected by DAPI staining. The percentage of Annexin V‑fluoroscein isothyiocyanate positive cells were 3.73, 17.61, 23.44 and 65.43% in HepG2 cells treated with 0, 40, 50 and 60 µM of 20(S)‑PPD, respectively. Furthermore, 20(S)‑PPD upregulated the expression of Bax and downregulated the expression of Bcl‑2 and also activated caspases‑3 and ‑9, and Poly [ADP‑ribose] polymerase cleavage. In addition, 20(S)‑PPD inhibited the phosphorylation of protein kinase B (Akt; Ser473). The results indicate that 20(S)‑PPD inhibits the viability of HepG2 cells and induces apoptosis in HepG2 cells by inhibiting the phosphoinositide‑3‑kinase/Akt pathway.

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