(+)-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 antiprolife-rative 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.

Quercetin alleviated H2O2‐induced apoptosis and steroidogenic impairment in goat luteinized granulosa cells

“…[ 3 ] PCNA, an essential DNA replication protein, was a cellular marker of cell multiplication. [ 30 ] CCND2 related to the cell cycle was also one of the cellular markers of cell proliferation. In the current study, forskolin treatment for 10 days downregulated the expression levels of CYP19A1, PCNA , and CCND2 , whereas it increased the expression of PTGFR ‐ and steroidogenesis‐related gene ( StAR, HSD3B , and P450scc ) and P 4 production, which was consistent with previous report, indicating the luteinization of goat GCs.…”

Terrein inhibits migration of human breast cancer cells via inhibition of the Rho and Rac signaling pathways

“…Terrein exhibits several biological activities including anti-inflammation, anti-melanogenesis, and anticancer properties. Treatment of keratinocytes, hepatoma and lung cell lines with terrein does not stimulate apoptosis (7,8), instead it appears to limit proliferation by promoting cell cycle arrest. Similarly, terrein also inhibited growth and induced cell cycle arrest in a human ovarian cancer cell line (9) and hepatoma Bel-7402 cells (8).…”

“…Treatment of keratinocytes, hepatoma and lung cell lines with terrein does not stimulate apoptosis (7,8), instead it appears to limit proliferation by promoting cell cycle arrest. Similarly, terrein also inhibited growth and induced cell cycle arrest in a human ovarian cancer cell line (9) and hepatoma Bel-7402 cells (8). However, the activity of terrein is cell type-dependent and this compound not only inhibits cell proliferation but also induces apoptosis.…”

Terrein performs antitumor functions on esophageal cancer cells by inhibiting cell proliferation and synergistic interaction with cisplatin

“…Previous studies have demonstrated that terrein has antiproliferative activity in a number of types of cancer (20)(21)(22)24). Cancer is an uncontrolled cell proliferation and death (12); therefore, inhibiting specific proteins that drive the cell cycle may be an efficient strategy to develop novel anticancer drugs.…”

“…Terrein may also inhibit cell proliferation and induce cell cycle arrest in human ovarian cancer cells (23). More recently, it has been revealed that terrein inhibited Bel-7402 human hepatoma cell proliferation through cell cycle arrest (24).…”