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(20S) Ginsenoside Rh2-Activated, Distinct Apoptosis Pathways in Highly and Poorly Differentiated Human Esophageal
He Li1,2, Chunxiao Han1,3, Chen Chen1
1Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, College of Life Science, Jilin University, Changchun 130012, China.
Abstract:
Ginsenoside Rh2 (G-Rh2), a rare ginsenoside isolated from red ginseng, has considerable anti-cancer activity and induces apoptosis in a variety of cancer cells, but its activity in esophageal cancer cells is unclear. In this study, we examined the cytotoxic activity of (20S) G-Rh2 in highly differentiated esophageal squamous ECA109 cells and poorly differentiated esophageal squamous TE-13 cells. (20S) G-Rh2 exerted intense cytotoxicity in ECA109 and TE-13 cells with an IC50 of 2.9 and 3.7 μg/mL, respectively. After treatment with G-Rh2, Bcl-2, and Bcl-xL, the two main anti-apoptosis Bcl-2 family proteins upregulated, and Bax and Bak, the two key pro-apoptosis proteins translocated to mitochondria in both cell lines. At the same time, cytochrome c and Smac released from mitochondria, followed by caspase-9 activation, indicating that a mitochondria-mediated intrinsic apoptosis pathway was activated in both cell lines upon treatment with (20S) G-Rh2. It is noteworthy that (20S) G-Rh2 upregulated the transcription and protein expression of two death receptors, Fas and DR5, and subsequently activated Caspase-8 in the TE-13 cells but not in the ECA109 cells. Taken together, we demonstrated the potent anti-esophageal cancer cell activity of (20S) G-Rh2 and showed its working mechanism in two differentiated esophageal cancer cells, which can provide important evidence for developing an effective strategy for anti-esophageal cancer treatment.
Insights
Ginsenoside Rh2 (G-Rh2) shows potent anti-cancer effects against esophageal cancer cells by inducing apoptosis. This study reveals its mechanism, offering hope for new esophageal cancer treatments.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Ginsenoside Rh2 (G-Rh2), derived from red ginseng, exhibits anti-cancer properties.
- Its efficacy and mechanism in esophageal cancer remain largely uninvestigated.
Purpose of the Study:
- To evaluate the cytotoxic effects of (20S) G-Rh2 on esophageal squamous cell carcinoma (ESCC) lines.
- To elucidate the apoptosis-inducing mechanisms of (20S) G-Rh2 in ESCC.
Main Methods:
- Assessed cytotoxicity of (20S) G-Rh2 in ECA109 and TE-13 esophageal cancer cell lines.
- Analyzed alterations in Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax, Bak) and mitochondrial apoptosis markers.
- Investigated the role of death receptors (Fas, DR5) and caspase activation.
Main Results:
- (20S) G-Rh2 demonstrated significant cytotoxicity against both ECA109 and TE-13 cells (IC50 values 2.9 and 3.7 μg/mL, respectively).
- G-Rh2 treatment induced mitochondrial-mediated intrinsic apoptosis by altering Bcl-2 family protein expression and promoting cytochrome c/Smac release.
- TE-13 cells showed activation of the extrinsic pathway via Fas/DR5 upregulation and Caspase-8 activation, unlike ECA109 cells.
Conclusions:
- (20S) G-Rh2 possesses potent anti-esophageal cancer activity.
- The compound effectively triggers apoptosis through both intrinsic and, in some cases, extrinsic pathways in esophageal cancer cells.
- These findings support the development of G-Rh2 as a therapeutic agent for esophageal cancer.
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