Downregulation of p-ERK1/2 and p-AKT expression by curcumin and tetrahydrocurcumin in hepatocellular carcinoma-induced tumors in nude mice

Background: Curcumin (CUR) and tetrahydrocurcumin (THC) inhibits tumor angiogenesis. It is suggested that tumor progress may be related to the pathway of extracellular signal-regulated kinase 1/2 (ERK1/2) and serine/threonine kinase AKT, but the mechanism remains unclear.

Objective: Investigate the effects of CUR and THC on the expression of ERK1/2 and AKT in hepatocellular carcinoma (HepG2)-induced tumors in nude mice.

Methods: The curcuminoid mixture was obtained from the rhizomes of Curcuma longa, which was subjected to silica gel column chromatography to afford CUR as the major constituent. THC was prepared by hydrogenation of curcumin with palladium on charcoal as a catalyst. HepG2-implanted nude mice model was used to study of angiogenesis and tumor progression. Expressions of phospho-ERK1/2 (p-ERK1/2) and phopho-AKT (p-AKT) in HepG2-implated tissue were measured by immunohistochemistry. Tumor area, area of expression and expression ratio of pERK1/2 and p-AKT were determined.

Results: Increases in p-ERK1/2 and p-AKT expression in HepG2 group was related to changes in tumor growth in control, CUR, and THC groups. THC-treatment could attenuate the p-ERK1/2, p-AKT expression, tumor area, and ratio of expression in HepG2-implanted nude mice significantly, compared to CUR-treatment.

Conclusion: HepG2-induced tumor progression may be inhibited by THC in part through the inhibition of mitogen-activated protein kinase (MEK)/ERK and phosphoinositide 3-kinase (PI3K)/AKT.