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Published on: October 27, 2020
Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway
Yajun Wang1, Jun Wu2, Biyun Lin3
1Department of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan, Guangdong 523808, China; Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China.
Abstract:
Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-β receptor/Smad pathway and increased TGF-β receptor I (RI), TGF-βRII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-β receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-β receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented galangin-induced apoptosis. Our findings indicate a novel mechanism for galangin-induced autophagy via activation of the TGF-β receptor/Smad pathway. The induction of autophagy thus reflects the anti-proliferation effect of galangin on HCC cells.
Insights
Galangin suppresses liver cancer (HCC) cell growth by triggering autophagy through the transforming growth factor-beta (TGF-β) receptor/Smad pathway. This process inhibits cancer cell proliferation and promotes apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Identifying novel therapeutic agents that target HCC proliferation is crucial.
- Galangin, a natural flavonoid, has shown potential anti-cancer properties.
Purpose of the Study:
- To elucidate the mechanism by which galangin suppresses HCC cell proliferation.
- To investigate the role of autophagy and the transforming growth factor-beta (TGF-β) receptor/Smad pathway in galangin's effects.
Main Methods:
- Investigated galangin's effect on HCC cell proliferation and autophagy.
- Analyzed the expression of TGF-β receptor/Smad pathway components (RI, RII, Smad1-4, Smad6-7).
- Utilized small interfering RNA (siRNA) for Smad4 and a TGF-β receptor inhibitor (LY2109761) to assess pathway dependency.
- Examined the impact of down-regulating autophagy-related genes (Beclin1, ATG16L, ATG12, ATG3) on cell proliferation and apoptosis.
Main Results:
- Galangin induced autophagy in HCC cells.
- Galangin modulated the TGF-β receptor/Smad pathway, increasing Smad1-4 and decreasing Smad6-7 levels.
- Inhibition of the TGF-β receptor/Smad pathway (via Smad4 siRNA or LY2109761) blocked galangin-induced autophagy.
- Down-regulation of key autophagy genes (Beclin1, ATG16L, ATG12, ATG3) reversed galangin's anti-proliferative and anti-apoptotic effects.
Conclusions:
- Galangin induces autophagy in HCC cells by activating the TGF-β receptor/Smad pathway.
- Autophagy induction is a key mechanism underlying galangin's anti-proliferative effect on HCC.
- This study reveals a novel therapeutic mechanism for galangin in HCC treatment.
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