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Published on: January 26, 2024
Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling
Jiaqi Su1, Xianbing Liu2, Xiaoyue Zhao3
1Department of Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China.
Background:
Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known.
Objectives:
To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article.
Methods:
The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells.
Results:
Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC.
Conclusion:
Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.
Insights
Curcumin suppresses hepatocellular carcinoma (HCC) by downregulating membrane-associated RING-CH 1 (MARCH1) and inhibiting the JAK2/STAT3 pathway. This research identifies MARCH1 as a potential therapeutic target for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- Curcumin exhibits potential anti-cancer properties, but its precise mechanisms in HCC are not fully understood.
Purpose of the Study:
- To investigate the role of membrane-associated RING-CH 1 (MARCH1) in curcumin's anti-HCC effects.
- To elucidate the molecular pathways involved in curcumin-induced growth suppression of HCC cells.
Main Methods:
- In vitro and in vivo experiments were conducted to assess curcumin's impact on HCC cell proliferation, apoptosis, and cell cycle.
- Expression levels of MARCH1, apoptosis-related proteins (Bcl-2), angiogenesis markers (VEGF), cell cycle regulators (cyclin B1, cyclin D1), and JAK2/STAT3 signaling molecules were measured.
- MARCH1 modulation via siRNA or overexpression was employed to determine its functional significance.
Main Results:
- Curcumin inhibited HCC cell proliferation, induced apoptosis, and caused G2/M cell cycle arrest, correlating with decreased Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 phosphorylation.
- MARCH1 expression was found to be high in HCC and downregulated by curcumin in a dose-dependent manner.
- MARCH1 knockdown mimicked curcumin's effects, while MARCH1 overexpression reversed them, indicating MARCH1's crucial role in curcumin's anti-tumor activity.
Conclusions:
- Curcumin suppresses HCC growth by downregulating MARCH1 expression, thereby inhibiting the JAK2/STAT3 signaling pathway.
- MARCH1 emerges as a novel therapeutic target for hepatocellular carcinoma treatment with curcumin.
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