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. 2018 May-Jun;32(3):549-554.
doi: 10.21873/invivo.11274.

Amentoflavone Inhibits ERK-modulated Tumor Progression in Hepatocellular Carcinoma In Vitro

Kun-Ching Lee  1   2 , Jai-Jen Tsai  3 , Chih-Wei Tseng  4 , Yu-Cheng Kuo  5   6 , Yao-Chen Chuang  7 , Song-Shei Lin  8 , Fei-Ting Hsu  9   10   11
Affiliations

Amentoflavone Inhibits ERK-modulated Tumor Progression in Hepatocellular Carcinoma In Vitro

Kun-Ching Lee et al. In Vivo. 2018 May-Jun.

Abstract

Background/aim: A previous study indicated that amentoflavone inhibits tumor growth of breast cancer. However, the anti-cancer effects and mechanism of amentoflavone in hepatocellular carcinoma (HCC) have not been elucidated. The aim of the present study was to verify the effect of amentoflavone on tumor progression in HCC.

Materials and methods: HCC SK-Hep1 cells were treated with different concentrations of amentoflavone or 10 μM PD98059 (extracellular signal-regulated kinases (ERK) inhibitor) for 48 h, respectively, and then cell viability, NF-κB activation, levels of tumor progression-associated proteins, and cell invasion were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene assay, western blotting, and cell invasion assay.

Results: The results demonstrated that both amentoflavone and PD98059 not only significantly reduced cell viability, NF-κB activation, and cell invasion, but also inhibited the expression of tumor progression-associated proteins. In addition, we found that amentoflavone suppresses ERK phosphorylation.

Conclusion: The results of the present study suggest that amentoflavone down-regulates ERK-modulated tumor progression in HCC.

Keywords: Amentoflavone; ERK; NF-κB; hepatocellular carcinoma.

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Figures

Figure 1
Figure 1. Effect of amentoflavone on cell viability and NF-ĸB activation in SK-Hep1 cells. Cells were treated with different concentrations (0-200 μM in 0.1% DMSO) of amentoflavone for 48 h. (A) Change of cell viability was evaluated with MTT assay. (B) NF-ĸB activation was determined with NF-ĸB reporter gene assay and corrected by using cell viability. *p<0.05 and **p<0.01 compared to control (0.1 % DMSO treatment)
Figure 2
Figure 2. Effect of PD98059 (ERK inhibitor) on cell viability and NF-ĸB activation in SK-Hep1 cells. Cells were treated with different concentrations (0-30 μM in 0.1% DMSO) of PD98059 for 48 h. (A) Change of cell viability was evaluated by using MTT assay, (B) NF-ĸB activation was investigated with NF-ĸB reporter gene assay and corrected by using cell viability. *p<0.05 and **p<0.01 compared to control (0.1 % DMSO treatment).
Figure 3
Figure 3. 3. Effect of PD98059 and amentoflavone on the expression of tumor progression-associated proteins in SK-Hep1 cells. Cells were treated with 10 μM PD98059, or different concentrations (0, 100, 200 μM) of amentoflavone for 48 h, respectively. Protein levels of MMP-9, XIAP, VEGF, cyclin-D1, and pERK were evaluated with western blotting assay. (A) PD98059 treatment, (B) Amentoflavone treatment.
Figure 4
Figure 4. Effect of PD98059 and amentoflavone on cell invasion in SK-Hep1 cells. Cells were treated with 10 μM PD98059, or different concertation (0, 100, 200 μM) of amentoflavone for 48 h, respectively. Invasive ability of SK-Hep1 cells was determined by using cell invasion assay. (A) PD98059 treatment, (B) Amentoflavone treatment. **p<0.01 as compared to control (0.1 % DMSO treatment).
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