Red American ginseng enhances the effect of fluorouracil on human colon cancer cells via both paraptosis and apoptosis pathways.

Introduction: As a commonly used chemotherapeutic agent, fluorouracil (5-FU) has serious dose-limiting side effects. In this study, we evaluated the synergy between red American ginseng (RAG) and 5-FU on human colorectal cancer cells, and explored the potential mechanisms.

Methods: Ginsenoside contents of white American ginseng (WAG) and RAG were determined by HPLC. Cell proliferation was evaluated by MTS assay. Combination Index (CI) analysis was executed using CompuSyn software. Paraptotic events were observed after crystal violet staining. Cell cycle distribution, cyclin A expression and apoptotic induction were analyzed using flow cytometry.

Results: We observed the heat treatment remarkably increased levels of ginsenoside Rg3, 20-Rg3, Rk1 and Rg5. When the combinations of 5-FU and RAG were applied, cell proliferation inhibition rates were notably increased, indicating that RAG significantly enhanced 5-FU's effect. Additionally, CI analysis suggested that there was a synergistic action of 5-FU and RAG when combined. The cell cycle data indicated 5-FU induced S phase arrest, and the combination of 5-FU and RAG increased G1 phase. Further, the RAG's ability to enhance the anti-cancer effects of 5-FU was linked to both paraptosis and apoptosis inductions.

Conclusion: RAG may have clinical utility to decrease the dosage of 5-FU in colorectal cancer therapeutics.