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Published on: August 23, 2019
Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns
Jing Cai1, Xiang-Li Zhao, An-Wen Liu
1Department of Oncology, Second Affiliated Hospital, Nanchang University, Nanchang, China.
Abstract:
Apigenin, a common plant flavonoid, has been shown to possess anti-tumor properties; however, the underlying molecular mechanisms are still not completely understood. In the present study, we investigated the effects of apigenin on human hepatoma Huh7 cell proliferation, cell cycle distribution, apoptosis, and colony formation in vitro, as well as on the tumorigenicity of Huh7 cells in vivo. To get more insight into the mechanism of apigenin action, we performed genome-wide expression profiling of apigenin-treated Huh7 cells using cDNA microarrays (Agilent Whole Human Genome Oligo Microarray) that contain 41,000 genes. Ten of the most differentially expressed genes (≧5-fold changes) were selected for further evaluation by quantitative RT-PCR (qPCR) and Western blot analyses. Notably, apigenin (5-20 μg/ml) remarkably inhibited Huh7 cell proliferation and colony formation as compared to the vehicle control, which was in a dose-dependent manner. Accompanying with the decreased growth, apigenin-treated cells showed a cell cycle arrest at G2/M phase and an increased rate of apoptosis. Moreover, the xenografts derived from Huh7 cells were significantly (p<0.05) retarded by the delivery of apigenin (50 μg/mouse/day) relative to the control counterparts. Gene expression profile analysis revealed that 1336 genes were up-regulated and 428 genes were down-regulated by apigenin. The down-regulation of interleukin-4 receptor and ubiquitin specific protease 18 and the up-regulation of SLC27A3 and chemokine (C-C motif) receptor 2 were further confirmed by the qPCR and Western blot results. In conclusion, apigenin exhibits inhibitory effects on hepatoma cell growth, which is likely mediated through alteration of gene expression profiles.
Insights
Apigenin, a plant flavonoid, inhibits hepatoma cell growth by altering gene expression. This study shows apigenin reduces proliferation, induces apoptosis, and arrests the cell cycle, offering potential anti-cancer strategies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Apigenin is a flavonoid with known anti-tumor properties.
- The molecular mechanisms of apigenin's anti-cancer effects are not fully understood.
Purpose of the Study:
- To investigate apigenin's effects on human hepatoma Huh7 cell proliferation, cell cycle, apoptosis, and tumorigenicity.
- To elucidate the molecular mechanisms underlying apigenin's anti-cancer activity through gene expression profiling.
Main Methods:
- In vitro studies on Huh7 cell proliferation, cell cycle, apoptosis, and colony formation.
- In vivo studies using xenografts to assess tumorigenicity.
- Genome-wide expression profiling using cDNA microarrays.
- Quantitative RT-PCR and Western blot analyses for gene validation.
Main Results:
- Apigenin significantly inhibited Huh7 cell proliferation and colony formation in a dose-dependent manner.
- Apigenin induced G2/M cell cycle arrest and increased apoptosis in Huh7 cells.
- Apigenin treatment significantly retarded xenograft tumor growth in vivo.
- Gene expression profiling revealed significant up-regulation and down-regulation of numerous genes, including IL-4 receptor, USP18, SLC27A3, and CCR2.
Conclusions:
- Apigenin exhibits significant inhibitory effects on hepatoma cell growth both in vitro and in vivo.
- The anti-cancer activity of apigenin is likely mediated by alterations in global gene expression profiles.
- Apigenin represents a promising therapeutic agent for hepatocellular carcinoma.
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