Theabrownin Induces Apoptosis and Tumor Inhibition of Hepatocellular Carcinoma Huh7 Cells Through ASK1-JNK-c-Jun
Jiaan Xu1,2, Bo Yan1,2, Lei Zhang3
1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Purpose:
Theabrownin (TB), a main pigment and bioactive component of tea, has been shown anti-tumor activities against carcinomas, but its effects on hepatocellular carcinoma (HCC) remain unclear.
Methods:
Hepatocellular carcinoma Huh7 cells were used for analyses. Cell viability assay was performed to determine TB's anti-proliferative effect, and flow cytometry with annexin V-FITC/PI double staining and DAPI staining were performed to determine its pro-apoptotic effect. Real-time PCR and Western blot assays were conducted to detect the molecular actions of TB. And a xenograft model of zebrafishes was established to evaluate the in vivo effect of TB. SP600125 (JNK inhibitor) was in vivo and in vitro used to verify the regulatory role of the JNK signaling pathway in the anti-hepatic carcinoma mechanism of TB.
Results:
TB exerted significant anti-proliferative and pro-apoptotic effects on Huh7 cells in a dose-dependent manner. The molecular data showed that TB up-regulated the gene expressions of NOXA, PUMA, P21, Bax, and Bim and up-regulated the protein expressions of ASK-1, Bax, phosphorylated JNK, and phosphorylated c-Jun with down-regulation of Bcl-2. The in vivo data showed that TB exerted significant tumor-inhibitory effect which was even stronger than that of cis-platinum. Furthermore, the JNK inhibitor significantly weakened TB's effects both in vivo and in vitro and blocked the related molecular pathway.
Conclusion:
TB exerts anti-proliferative, pro-apoptotic, and tumor-inhibitory effects on Huh7 cells through activation of the JNK signaling pathway. For the first time, this study provides new evidence of anti-HCC effects and mechanism of TB.
Insights
Theabrownin (TB) effectively inhibits hepatocellular carcinoma (HCC) cell growth and promotes apoptosis by activating the JNK signaling pathway. This study reveals TB
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Theabrownin (TB), a key tea pigment, exhibits anti-tumor properties.
- The effects of TB on hepatocellular carcinoma (HCC) are not well understood.
Purpose of the Study:
- To investigate the anti-cancer effects of TB on HCC cells.
- To elucidate the molecular mechanisms underlying TB's action in HCC.
Main Methods:
- In vitro studies using Huh7 HCC cells assessed TB's effects on cell viability and apoptosis.
- Molecular analyses included real-time PCR and Western blotting to examine gene and protein expression.
- In vivo efficacy was evaluated using a zebrafish xenograft model, with JNK pathway inhibition used to confirm mechanism.
Main Results:
- TB demonstrated significant dose-dependent anti-proliferative and pro-apoptotic effects on Huh7 cells.
- TB modulated key apoptosis-related genes (NOXA, PUMA, P21, Bax, Bim) and proteins (ASK-1, Bax, p-JNK, p-c-Jun, Bcl-2).
- In vivo, TB exhibited potent tumor inhibition, surpassing cis-platinum, via JNK pathway activation.
Conclusions:
- Theabrownin (TB) effectively inhibits hepatocellular carcinoma (HCC) cell proliferation and induces apoptosis.
- TB's anti-cancer activity is mediated through the activation of the JNK signaling pathway.
- This study provides novel evidence for TB's therapeutic potential against HCC.
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