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Gamma-tocotrienol Inhibits Proliferation and Growth of HSD17B4 Overexpressing HepG2 Liver Cancer Cells
Xiaoming Wang1,2, Xijia Liang3, Nan Zhang1,4
1Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Introduction:
Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC).
Aims:
This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells.
Methods:
HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored.
Results:
HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors.
Conclusion:
In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.
Insights
Gamma-tocotrienol (γ-T3) inhibits hepatocellular carcinoma (HCC) cell growth by interacting with HSD17B4, reducing proliferation and promoting apoptosis. This study highlights γ-T3
Area of Science:
- Hepatocellular Carcinoma Research
- Molecular Biology
- Cancer Therapeutics
Background:
- Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) plays a role in hepatocellular carcinoma (HCC) progression.
- Overexpression of HSD17B4 promotes hepatocellular carcinoma cell proliferation.
Purpose of the Study:
- To investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on HSD17B4-overexpressing HepG2 cells.
- To explore the therapeutic potential of γ-T3 in HCC treatment.
Main Methods:
- HepG2 cells were transfected with HSD17B4 plasmids and treated with vitamin E (VE) or γ-T3.
- Cell proliferation, apoptosis, protein, and mRNA levels were assessed using MTS assay, flow cytometry, Western blotting, and qRT-PCR.
- In vivo tumor xenograft models were used to evaluate anti-tumor effects.
Main Results:
- γ-T3 dose-dependently inhibited proliferation of HSD17B4-overexpressing HepG2 cells.
- γ-T3 interacted with HSD17B4, inhibiting its enzymatic activity and reducing cyclin D1 expression.
- γ-T3 promoted apoptosis and suppressed key proliferation signaling pathways (ERK, MEK, AKT, STAT3).
- γ-T3 significantly reduced tumor growth in vivo.
Conclusions:
- γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HSD17B4-overexpressing HCC cells.
- γ-T3 demonstrates therapeutic potential for HCC by targeting HSD17B4-associated pathways.
- γ-T3 inhibits tumor growth and enhances apoptosis in HCC.
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