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Gintonin-Enriched Panax ginseng Extract Fraction Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis through
Seongwoo Hong1, Rami Lee2, Gyun Seok Park3
1Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on the viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression, notably, the decreased expression of the Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. This study demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.
Insights
Gintonin-enriched Panax ginseng extract fraction (GEF) sensitizes human renal cell carcinoma (RCC) cells to TRAIL-induced apoptosis. This combination therapy enhances cancer cell death by upregulating death receptors and modulating apoptotic proteins.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise in cancer therapy due to selective apoptosis induction in cancer cells.
- Resistance to TRAIL-induced apoptosis is a significant challenge in treating various cancers.
- Gintonin-enriched Panax ginseng extract fraction (GEF) possesses diverse pharmacological properties.
Purpose of the Study:
- To investigate the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells.
- To determine if GEF pre-treatment can overcome TRAIL resistance in RCC.
- To elucidate the molecular mechanisms underlying GEF's sensitization of RCC cells to TRAIL.
Main Methods:
- In vitro assessment of GEF's effects on RCC cell viability, clonogenic potential, and migration.
- Analysis of TRAIL-induced apoptotic signaling pathways following GEF pre-treatment.
- Evaluation of death receptor (DR4/5) and apoptotic protein expression levels.
- Inhibition of caspase activation using Z-VAD-FMK to confirm its role in apoptosis.
Main Results:
- GEF pre-treatment significantly sensitized RCC cells to TRAIL-induced apoptosis, indicated by DNA fragmentation.
- GEF inhibited RCC cell proliferation, colony formation, and migration.
- Sensitization correlated with upregulation of death receptors 4 and 5 (DR4/5) and decreased expression of a novel anti-apoptotic protein (Mu-2-related death-inducing gene).
- Caspase activation was essential for GEF/TRAIL-induced apoptosis.
Conclusions:
- GEF effectively sensitizes human RCC cells to TRAIL-induced apoptosis.
- The mechanism involves upregulation of DR4/5 and modulation of apoptotic protein expression.
- GEF represents a promising adjunct therapy to overcome TRAIL resistance in cancer treatment.
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