Amentoflavone Inhibits Hepatocellular Carcinoma Progression Through Blockage of ERK/NF-ĸB Activation

Kun-Ching Lee; Wei-Ting Chen; Yu-Chang Liu; Song-Shei Lin; Fei-Ting Hsu

doi:10.21873/invivo.11351

Amentoflavone Inhibits Hepatocellular Carcinoma Progression Through Blockage of ERK/NF-ĸB Activation

In Vivo. 2018 Sep-Oct;32(5):1097-1103. doi: 10.21873/invivo.11351.

Authors

Kun-Ching Lee^{1

2}, Wei-Ting Chen^{1

3}, Yu-Chang Liu^{1

2}, Song-Shei Lin⁴, Fei-Ting Hsu^{5

6

7

8}

Affiliations

¹ Department of Medical Imaging and Radiological Sciences, Central-Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
² Department of Radiation Oncology, National Yang-Ming University Hospital, Yilan, Taiwan, R.O.C.
³ Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.
⁴ Department of Medical Imaging and Radiological Sciences, Central-Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C. sslin@ctust.edu.tw sakiro920@gmail.com.
⁵ Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C. sslin@ctust.edu.tw sakiro920@gmail.com.
⁶ Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.
⁷ Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
⁸ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, R.O.C.

Abstract

Aim: The aim of the present study was to confirm therapeutic efficacy and find probable mechanism of action of amentoflavone in hepatocellular carcinoma (HCC) in vivo.

Materials and methods: Luciferase reporter vector pGL4.50_transfected SK-Hep1 (SK-Hep1/luc2) tumor-bearing mice were treated with vehicle or amentoflavone (100 mg/kg/day by gavage) for 14 days. Tumor growth, amentoflavone toxicity, and extracellular signal-regulated kinase (ERK)/nuclear factor-kappaB (NF-ĸB) signaling in tumor progression were evaluated with digital caliper, bioluminescence imaging, computed tomography, body weight, pathological examination of liver, and immunohistochemistry staining.

Results: Amentoflavone significantly inhibited tumor growth, ERK/NF-ĸB activation, and expression of tumor progression-associated proteins as compared to vehicle-treated group. In addition, body weight and liver morphology of mice were not influenced by amentoflavone treatment.

Conclusion: These results suggest that amentoflavone inhibits HCC progression through suppression of ERK/NF-ĸB signaling.

Keywords: Amentoflavone; bioluminescence imaging; extracellular signal-regulated kinase; hepatocellular carcinoma; nuclear factor-kappaB.

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Biflavonoids / pharmacology*
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Disease Models, Animal
Disease Progression
Extracellular Signal-Regulated MAP Kinases / metabolism*
Genes, Reporter
Humans
Immunohistochemistry
Liver Neoplasms / drug therapy
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Mice
Molecular Imaging
NF-kappa B / metabolism*
Signal Transduction / drug effects*
Tumor Burden / drug effects
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Biflavonoids
NF-kappa B
amentoflavone
Extracellular Signal-Regulated MAP Kinases