γ-terpinene inhibits the progression of hepatocellular carcinoma by regulating the PTEN/PI3K/Akt signaling pathway mediated glycolysis

Hepatocellular carcinoma (HCC) is a lethal malignancy. This study was designed to investigate the anti-HCC effects of the natural monoterpene compound γ-terpinene (γ-TPN) and its potential mechanism regulating the PTEN/PI3K/Akt pathway and glycolysis. The effects of γ-TPN on cell proliferation, migration, and invasion were assessed in vitro using EdU, colony formation, and Transwell assays. Western blotting and biochemical assay kits were employed to detect PTEN/PI3K/Akt pathway proteins and glycolytic indicators. Rescue experiments with the PTEN inhibitor bpV verified PTEN’s essential role. Finally, a subcutaneous xenograft tumor model in nude mice was established to confirm γ-TPN’s antitumor efficacy and underlying mechanism in vivo. In vitro experiments demonstrated that γ-TPN dose-dependently inhibited HCC cell proliferation, migration, and invasion. Mechanistically, γ-TPN suppressed the PI3K/Akt pathway by upregulating PTEN, which subsequently downregulated key glycolytic proteins and reduced glucose consumption, ATP production, and lactate generation. These effects were reversed by the PTEN inhibitor bpV. In vivo studies confirmed that γ-TPN markedly inhibited tumor growth and Ki67 expression, consistently suppressing the PTEN/PI3K/Akt pathway and glycolysis in tumor tissues. Collectively, γ-TPN inhibits HCC progression through PTEN upregulation, which suppresses the PI3K/Akt pathway and its associated glycolytic metabolism.