Lupeol enhances radiosensitivity of human hepatocellular carcinoma cell line SMMC-7721 in vitro and in vivo

Abstract

Purpose: To investigate the effect of lupeol, a pentacyclictriterpene, on the radiosensitivity of a human hepatocellular carcinoma (HCC) in vitro and in vivo xenografts.Methods: SMMC-7721 cells were exposed to γ-radiation with or without lupeol and assayed for proliferation, clonogenic survival, apoptosis and cell cycle distribution. The cells were also analyzed by Western blotting for the expression levels of the proteins involved in apoptosis. Finally radiosensitization by lupeol was assessed in HCC xenograft model.Results: Lupeol further suppressed the proliferation and colonogenic survival of the SMMC-7721 cells exposed to γ-radiation. It could also induce the accumulation of cells in G2/M phase together with γ-radiation. The data also indicated that lupeol sensitized SMMC-7721 cells exposed to γ-radiation to apoptosis and activated the apoptotic proteins including caspase-9 and PARP. Administration of lupeol with radiation in HCC xenograft model produced a significant tumor growth delay compared with radiation or lupeol alone and was well tolerated.Conclusion: Lupeol significantly enhanced the radiosensitivity of SMMC-7721 cells in vitro and in vivo. The mechanisms involved could be cell cycle arrest and induction of apoptosis. Our studies suggest that lupeol has the potential to be developed as an adjuvant for radiotherapy in HCC.