Jin-Yi Wan1,2,3, Haiqiang Yao2,3, Chun-Feng Zhang2,3, Wei-Hua Huang2,3, Qihui Zhang2,3, Zhi Liu2,3, Yi Bi2,3, Stephanie Williams2,3, Chong-Zhi Wang2,3, Chun-Su Yuan2,3,4. 1. School of Pharmacy, Jiangsu University, Zhenjiang, JS 212013, China. 2. Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA. 3. Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA. 4. Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, USA.
Abstract
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.
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.
Entities:
Keywords:
Apoptosis; Cell cycle; Fluorouracil; Paraptosis; Red American ginseng; colorectal cancer
Authors: C H Smorenburg; G J Peters; C J van Groeningen; P Noordhuis; K Smid; A M G H van Riel; W Dercksen; H M Pinedo; G Giaccone Journal: Ann Oncol Date: 2005-10-26 Impact factor: 32.976