Magnolol Induces Apoptosis and Inhibits ERK-modulated Metastatic Potential in Hepatocellular Carcinoma Cells

Abstract

Background/Aim: The aim of the present study was to evaluate the anti-cancer effect of magnolol in hepatocellular carcinoma (HCC) cells in vitro. Materials and Methods: HCC SK-Hep1 cells were treated with different concentrations of magnolol or PD98059 [extracellular-signal-regulated kinase (ERK) inhibitor] for 48 h, and then cell viability, apoptosis, signal transduction, expression of anti-apoptotic and metastasis-related proteins, and cell invasion were investigated by [3][4]-2,5-diphenyltetrazolium bromide] (MTT) assay, flow cytometry, nuclear factor kappa B (NF-ĸB) reporter gene, western blotting, and cell invasion assays. Results: Magnolol significantly induced accumulation of sub-G 1 phase and caspase-3 activation and inhibited NF-ĸB activation, cell invasion, expression of phosphorylated ERK (pERK), anti-apoptotic and metastatic-related proteins. ERK inactivation was required for magnolol-induced inhibition of metastatic potential of SK-Hep1 cells. Conclusion: Taken together, these results indicated that magnolol not only induced apoptosis, but also inhibited ERK-modulated metastatic potential of HCC SK-Hep1 cells.

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

“…However, MM1 displayed a significantly stronger inhibitory effect on cell growth than magnolol at similar concentrations, indicating a greater tumor-suppressive activity than that of magnolol ( Figures 1C-F). The half-maximal inhibitory concentration (IC 50 ) of magnolol toward Huh7 and HepG2 cells was ∼97 and 65 µM, respectively, which is similar to results from other studies (46)(47)(48), while the IC 50 of MM1 in Huh7 and HepG2 cells was 48 and 61 µM, respectively. Moreover, only a slight inhibitory effect was observed on the growth of the HFB cell line at the highest concentrations of magnolol and MM1 ( Figure 1B).…”

Astragaloside IV Induces Apoptosis, G1-Phase Arrest and Inhibits Anti-apoptotic Signaling in Hepatocellular Carcinoma

“…Overexpression of antiapoptotic proteins (XIAP, MCL1, C-FLIP, and Survivin) has the capacity to attenuate therapeutic efficacy of anticancer agents via blocking intrinsic and extrinsic pathway-mediated apoptosis. The reduced expression of anti-apoptotic proteins was associated with favorable prognosis in patients with HCC (18,25). Cyclin-dependent kinases (CDK)4/6 inhibitors disrupt cell-cycle progression by inducing G 1 phase arrest in different types of cancer (15).…”

“…Cells were finally centrifuged and stained by propidium iodide staining solution (BD Pharmingen™, Franklin Lakes, NJ, USA) in the dark at 37˚C for 30 min. The cell-cycle distribution was then acquired by flow cytometry (FACSCalibur; Becton-Dickinson, Franklin Lakes, NJ, USA) and quantified by FlowJo 7.6.1 system (18).…”

The In Vivo Radiosensitizing Effect of Magnolol on Tumor Growth of Hepatocellular Carcinoma

“…ERK, a member of activated protein kinase (MAPK) family, is the downstream component of RAF/mitogen-activated protein/ERK kinase (MEK)/ERK signaling pathway involved in tumor progression (23). ERK has been demonstrated to regulate expression of proliferation, anti-apoptotic, and invasion-related proteins through activation of the NF-ĸB signaling in HCC (10,20). Furthermore, radioresistance of cancer cells has been linked to the phosphorylation of ERK (24).…”

“…Induction of mitochondrial apoptosis, arrest of cell cycle G 2 /M phase, and inhibition of in vivo 34: 1789-1796 (2020) NF-ĸB activation have been associated with the radiosensitizing effect of natural products in HCC (7)(8)(9). Magnolol, one of major components of Magnolia officinalis, has been shown to trigger apoptosis through death receptor (extrinsic)/mitochondrial (intrinsic) pathways and to downregulate extracellular signal-regulated kinase (ERK)/NF-ĸB signaling in HCC in vitro and in vivo (10,11). Magnolol was also recognized to have an anti-inflammation and anti-tumor potential (12).…”