(+)-Terrein inhibits human hepatoma Bel-7402 proliferation through cell cycle arrest

Abstract

Hepatoma is a common malignant tumor. Thus, the development of a high-efficacy therapeutic drug for hepatoma is required. In this study, (+)-terrein isolated from the marine sponge-derived Aspergillus terreus PF-26 against cell growth, apoptosis and cell cycle were assessed by MTT and flow cytometry. mRNA array containing 73 cell cycle-related genes and three cell morphology-related genes was generated and its performance evaluated. The cell cycle pathway map was created using the pathview package. The results showed that (+)-terrein inhibited the growth of Bel-7402 cells with alterations in cell morphology and a reduced transcript expression of cell morphology genes (fibronectin, N-cadherin, and vimentin). In addition, flow cytometric analysis revealed that (+)-terrein arrested the Bel-7402 cell cycle without inducing apoptosis. Based on multiple mRNA analysis, the downregulated expression of the CCND2, CCNE2, CDKN1C, CDKN2B, ANAPC, PKMYT1, CHEK2 and PCNA genes was observed in 10 μM (+)-terrein-treated Bel-7402 cells (>2-fold and P≤0.05), compared with the controls. Thus, the antiproliferative mechanism of (+)-terrein against Bel-7402 cells may be due to the cell cycle arrest by blocking cell cycle gene expression and changing cell morphology.