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20(s)-ginsenoside Rh2 promotes TRAIL-induced apoptosis by upregulating DR5 in human hepatocellular carcinoma cells
Wenmo Liu1, Siqi Wang1, Qinchuan Yang1
1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand is a potential therapeutic anti-cancer drug with selective cytotoxicity in cancer cells. However, in multiple clinical trials, the therapeutic effect of TRAIL is limited owing to tumor resistance. The combination of small molecules or other drugs may represent a suitable strategy to overcome TRAIL resistance. This study found that 20(s)-ginsenoside Rh2 sensitized non-sensitive human hepatocellular carcinoma cells to TRAIL-induced apoptosis. The combination of TRAIL and Rh2 decreased cell viability and increased caspase cascade-induced apoptosis in several liver cancer cell lines. Moreover, we found that Rh2 reduced the apoptosis-related protein XIAP and Survivin, a negative regulator of the apoptosis pathway. At the same time, Rh2 can further enhance TRAIL-induced apoptosis by upregulating the death receptor 5, thereby significantly enhancing its anti-tumor effect. Furthermore, Rh2 enhanced the therapeutic efficacy of TRAIL in mouse xenograft models, suggesting that Rh2 also sensitizes TRAIL in vivo. Taken together, our study indicates that Rh2 may act as a sensitizer in combination with TRAIL to increase the efficacy of its anti-tumor activity.
Insights
The study shows that 20(s)-ginsenoside Rh2 (Rh2) can sensitize liver cancer cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) therapy. This combination enhances anti-tumor effects by reducing resistance and promoting apoptosis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent.
- Tumor resistance limits the clinical efficacy of TRAIL therapy.
- Combining TRAIL with other agents may overcome resistance.
Purpose of the Study:
- To investigate the potential of 20(s)-ginsenoside Rh2 (Rh2) as a sensitizer to TRAIL therapy in hepatocellular carcinoma.
- To elucidate the molecular mechanisms underlying Rh2's sensitization effect.
Main Methods:
- Hepatocellular carcinoma cell lines were treated with TRAIL alone or in combination with Rh2.
- Cell viability, apoptosis, and expression of apoptosis-related proteins (XIAP, Survivin, death receptor 5) were assessed.
- In vivo efficacy was evaluated using mouse xenograft models.
Main Results:
- Rh2 sensitized non-sensitive liver cancer cells to TRAIL-induced apoptosis.
- The combination of TRAIL and Rh2 decreased cell viability and enhanced caspase cascade activation.
- Rh2 downregulated XIAP and Survivin, and upregulated death receptor 5.
- Rh2 enhanced TRAIL's anti-tumor efficacy in vivo.
Conclusions:
- 20(s)-ginsenoside Rh2 acts as a potent sensitizer for TRAIL therapy in hepatocellular carcinoma.
- Rh2 enhances TRAIL efficacy by modulating apoptosis regulators and death receptors.
- The combination of TRAIL and Rh2 holds promise for overcoming TRAIL resistance in liver cancer treatment.
