Paradol Inhibits Proliferation and Migration of Human Hepatocellular Carcinoma Cells

Hepatocellular carcinoma is the most frequent primary liver cancer leading to a major health problem worldwide, with a lack of effective therapies after diagnosis. Paradol, a phenolic compound found in ginger, displayed bioactivities such as anti-oxidant, inhibition of promyelocytic leukemia cells and oral squamous carcinoma cells, while its effects on human hepatocellular carcinoma cells are unknown. Here, the cytotoxicity of paradol against hepatocellular carcinoma cell was investigated, as well as the underlying signaling pathways. By CCK-8 assay and transwell migration assay, paradol was found to reduce HepG2 cell viability and migration effectively, with IC50 of 35.87 mu M at 24 h. By cell cycle analysis and western blot, the accumulation of cells in G0/G1 phase and the downregulation of CCND1 and CCNE1 have proved the contribution of G0/G1 arrest for the cytotoxicity against HepG2 cells. Further, apoptotic death was demonstrated in HepG2 cells treated with paradol, by DAPI staining, Annexin-FITC/PI staining followed by flow cytometry and western blot for Bcl-2 and Bax. For signaling mechanism, the western blot data presented elevated p38 MAPK and JNK activation after paradol treatment. In summary, we have discovered paradol as a potential agent against hepatocellular carcinoma. It could inhibit proliferation and migration, partly through inducing apoptosis by G0/G1 phase arrest in hepatocellular carcinoma HepG2 cells, via MAPK signaling.