J Appl Biomed 16:311-319, 2018 | DOI: 10.1016/j.jab.2018.05.002

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

Jin-Yi Wan^a,b,c, Haiqiang Yao^b,c, Chun-Feng Zhang^b,c, Wei-Hua Huang^b,c, Qihui Zhang^b,c, Zhi Liu^b,c, Yi Bi^b,c, Stephanie Williams^b,c, Chong-Zhi Wang^b,c,*, Chun-Su Yuan^b,c,d

^a Jiangsu University, School of Pharmacy, Zhenjiang, China

^b University of Chicago, Tang Center for Herbal Medicine Research, Chicago, USA

^c University of Chicago, Department of Anesthesia and Critical Care, Chicago, USA

^d University of Chicago, Comprehensive Cancer Center, Chicago, USA

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, 20R-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.

Keywords: Red American ginseng; Fluorouracil; Colorectal cancer; Cell cycle; Paraptosis; Apoptosis

Received: October 3, 2017; Revised: April 14, 2018; Accepted: May 16, 2018; Published: November 1, 2018  Show citation