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

Lin-Yen Kuan; Wei-Lung Chen; Jiann-Hwa Chen; Fei-Ting Hsu; Tsu-Te Liu; Wei-Ting Chen; Kai-Lee Wang; Wen-Chang Chen; Yu-Chang Liu; Wei-Shu Wang

doi:10.21873/invivo.11387

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

In Vivo. 2018 Nov-Dec;32(6):1361-1368. doi: 10.21873/invivo.11387.

Authors

Lin-Yen Kuan^{1

2}, Wei-Lung Chen^{1

2}, Jiann-Hwa Chen^{1

2}, Fei-Ting Hsu³, Tsu-Te Liu⁴, Wei-Ting Chen⁵, Kai-Lee Wang⁶, Wen-Chang Chen^{7

8}, Yu-Chang Liu^{9

10

11}, Wei-Shu Wang^{12

13}

Affiliations

¹ Department of Emergency Medicine, Cathay General Hospital, Taipei, Taiwan, R.O.C.
² School of Medicine, Fu Jen Catholic University, Taipei, Taiwan, R.O.C.
³ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
⁴ Division of Gastroenterology, Department of Internal Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.
⁵ Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.
⁶ Department of Nursing, Ching Kuo Institute of Management and Health, Keelung, Taiwan, R.O.C.
⁷ Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi Branch, Chang Gung University of Science and Technology, Chiayi, Taiwan, R.O.C.
⁸ Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
⁹ Department of Medical Imaging and Radiological Science, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C. kevinyc.liu@gmail.com 11313@ymuh.ym.edu.tw.
¹⁰ Department of Radiation Oncology, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.
¹¹ Department of Radiation Oncology, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
¹² Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C. kevinyc.liu@gmail.com 11313@ymuh.ym.edu.tw.
¹³ School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.

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-(4,5-Dimethylthiazol-2-yl)-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-G₁ 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.

Keywords: Magnolol; apoptosis; extracellular-signal-regulated kinase; hepatocellular carcinoma.

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Apoptosis / genetics
Biphenyl Compounds / pharmacology*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lignans / pharmacology*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
NF-kappa B / metabolism
Phosphorylation / drug effects
Signal Transduction / drug effects

Substances

Antineoplastic Agents, Phytogenic
Biphenyl Compounds
Lignans
NF-kappa B
magnolol
Extracellular Signal-Regulated MAP Kinases