2-O-Methylmagnolol, a Magnolol Derivative, Suppresses Hepatocellular Carcinoma Progression via Inhibiting Class I Histone Deacetylase Expression

Abstract

Magnolia officinalis is widely used in Southeast Asian countries for the treatment of fever, headache, diarrhea, and stroke. Magnolol is a phenolic compound extracted from M. officinalis, with proven antibacterial, antioxidant, anti-inflammatory, and anticancer activities. In this study, we modified magnolol to synthesize a methoxylated derivative, 2-O-methylmagnolol (MM1), and investigated the use of MM1, and magnolol in the treatment of liver cancer. We found that both magnolol and MM1 exhibited inhibitory effects on the growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines and halted the cell cycle at the G1 phase. MM1 also demonstrated a substantially better tumor-suppressive effect than magnolol. Further analysis suggested that by inhibiting class I histone deacetylase expression in HCC cell lines, magnolol and MM1 induced p21 expression and p53 activation, thereby causing cell cycle arrest and inhibiting HCC cell growth, migration, and invasion. Subsequently, we verified the significant tumor-suppressive effects of magnolol and MM1 in an animal model. Collectively, these findings demonstrate the anti-HCC activities of magnolol and MM1 and their potential for clinical use.

Potential roles and molecular mechanisms of phytochemicals against cancer

“…MM1 represses class I histone deacetylase (HDAC) expression to activate p21 and p53, thus suppressing cell growth, migration, and invasion, and it shows better anti-tumor effects than magnolol in HCC cell lines. 66 Salidroside, a bioactive phenolic glycoside extracted from rhodiola crenulata, inacti- Food & Function Review vates the janus kinase 2 (JAK2)/STAT3 pathway to inhibit osteosarcoma MG63 and U2OS cell growth and invasion. It also suppresses the JAK2/STAT3 signaling pathway to activate the caspase-9-dependent apoptotic pathway and inhibit cell invasion in osteosarcoma cells.…”

Effect of enzyme-response Mag@CMCS@CPSG film on rice sheath blight disease (caused by Rhizoctonia solani) control and rice quality

“…. with previous methods to improve the stability and water solubility of magnolol by preparing drug-carrying particles or synthetic derivatives (Chen et al, 2020;Liu et al, 2022;Qu et al, 2023), the Mag@CMCS@CPSG film achieves accurate delivery of magnolol.…”

Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy

“…Methoxylated magnolol seems to possess enhanced anti-inflammatory activity. 2-o-methylmagnolol (Table 5 , 25 ) was found to up-regulate the lncRNA growth arrest specific 5 (GAS5), promote the apoptosis of skin cancer cells, and improve anti-tumor activity against these cells [ 128 , 129 ]. Honokiol (Table 5 , 26 ), an isomer of magnolol, has antitumor effects on various types of cancer.…”