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Silymarin suppresses HepG2 hepatocarcinoma cell progression through downregulation of Slit-2/Robo-1 pathway
Nuriye Ezgi Bektur Aykanat1, Sedat Kacar2, Serife Karakaya2
1Department of Histology and Embryology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. nebektur@ogu.edu.tr.
Background:
14 million people are diagnosed with new cancer and approximately 8 million people die from cancer every year. Hepatocellular carcinoma is the most common type of liver cancer and covers almost 5-6% of cancer deaths worldwide. Silybum marianum, a plant that contains silymarin, has been used traditionally in the treatment of liver diseases for centuries. The antioxidant, anti-inflammatory and anti-fibrotic anti-cancer properties of silymarin have been demonstrated in several studies in vivo and in vitro. The Slit/Robo signaling pathway plays a role in many processes such as neurogenesis, angiogenesis, cell proliferation, cell movement, cancer progression, cell invasion, migration and metastasis. In this study, we aimed to investigate the effects of silymarin on HepG2 Hepatocellular carcinoma cells on Slit-2/Robo-1 signaling pathway and CXCR-4 which plays a role in the metastasis process.
Methods:
HepG2 Hepatocellular carcinoma cells were used in the study. Different doses of silymarin's effect on HepG2 cells were observed by hematoxylin and eosin staining. Immunoblotting techniques were used to test the expression of Slit-2/Robo-1 and CXCR4 protein level. Immunocytochemistry was used to visualize the localization of Slit-2/Robo-1 and CXCR4 protein within the cells.
Results:
Silymarin caused apoptosis in HepG2 cells, decreased the level of CXCR-4 protein dose-dependently, and decreased the Slit-2/Robo-1 protein level at low doses and increased it at high doses.
Conclusions:
Silymarin doses showed anti-carcinogenic, anti-metastatic and apoptotic effects in a dose-dependent manner on HepG2 cells through the Slit-2/Robo-1 pathway.
Insights
Silymarin, derived from milk thistle, demonstrated anti-cancer effects on liver cancer cells. It induced apoptosis and affected metastasis-related proteins, suggesting therapeutic potential.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide.
- Silybum marianum (milk thistle) contains silymarin, traditionally used for liver ailments.
- Silymarin exhibits antioxidant, anti-inflammatory, and anti-cancer properties.
Purpose of the Study:
- To investigate silymarin's effects on HepG2 hepatocellular carcinoma cells.
- To analyze silymarin's impact on the Slit-2/Robo-1 signaling pathway.
- To evaluate silymarin's influence on CXCR-4 expression, a key metastasis marker.
Main Methods:
- HepG2 cells were treated with varying silymarin doses.
- Hematoxylin and eosin staining assessed cellular effects.
- Immunoblotting and immunocytochemistry analyzed Slit-2/Robo-1 and CXCR4 protein levels and localization.
Main Results:
- Silymarin induced apoptosis in HepG2 cells in a dose-dependent manner.
- Silymarin decreased CXCR-4 protein levels dose-dependently.
- Silymarin modulated Slit-2/Robo-1 protein levels, decreasing them at low doses and increasing them at high doses.
Conclusions:
- Silymarin exhibits dose-dependent anti-carcinogenic and anti-metastatic effects on HepG2 cells.
- The Slit-2/Robo-1 pathway is implicated in silymarin's anti-cancer activity.
- Silymarin promotes apoptosis in liver cancer cells via modulation of key signaling pathways.
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