Hispolon from Phellinus linteus Induces G0/G1 Cell Cycle Arrest and Apoptosis in NB4 Human Leukaemia Cells

Abstract

Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.

The anticancer effects of hispolon on lung cancer cells

“…Several studies have demonstrated that hispolon blocks cell cycle progression at the G0/G1 [12,20] or G2/M [21] phase, which depends on the cell context. Similarly, hispolon inhibits cell cycle progression and induces cell cycle arrest in G0/G1 phase in A549 and H661 cells.…”

“…To determine the effect of hispolon on the cell viability of nonsmall cell lung cancer cells, A549 or H661 cells were treated with various concentrations of hispolon (0, 5, 10, 20, 40, 80 and 160 lM) for different time periods (12,24, 48 and 72 h). Cells with 0.1% DMSO were served as a control.…”

“…Hispolon has hepatoprotective [6], anti-inflammatory [7], antimetastatic [8], and antiproliferative effects [9]. The antitumor activity of this phenol compound (hispolon) has attracted many attentions [8][9][10][11][12]. It has been shown that hispolon exhibits anticancer effects through inhibition of cell growth, induction of cell cycle arrest, and suppression of metastasis in various types of cancer cells [8][9][10][11][12].…”

Anti-inflammatory activity of Sanghuangporus sanghuang by suppressing the TLR4-mediated PI3K/AKT/mTOR/IKKβ signaling pathway

“…A recent study reported that sanghuang has moderate pharmacological activity: it enhances immunity, antitumor, 15,16 antiinammatory, [16][17][18] antioxidant activity; [16][17][18] and hepatoprotective effects; 19 among others. According to a research report, the active compounds in the sanghuang fruiting body include polysaccharides, triterpenoids, pyran and furan ketones, and polyphenolic compounds.…”

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

“…In addition, HPL has demonstrated antitumor effects in various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer and gastric cancer cells (16)(17)(18)(19)(20).…”