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TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol
Zhiyu Zhang1, Zejuan Li2, Xiaohui Wu1
1Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
Abstract:
Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.
Insights
Protopanaxadiol (PPD), a compound from American ginseng, effectively inhibits colon cancer growth in vivo and in vitro. It works by inducing apoptosis and regulating the TRAIL pathway, making it a promising therapeutic agent.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- American ginseng contains bioactive compounds with anticancer properties.
- Protopanaxadiol (PPD) exhibits significant anticancer potential among ginseng saponins.
Purpose of the Study:
- To investigate the in vivo and in vitro anticancer effects of PPD.
- To elucidate the molecular mechanisms underlying PPD's action in colorectal cancer.
Main Methods:
- In vivo mouse cancer model and human colorectal cancer cell lines (HCT-116) were used.
- Gene expression profiling was performed using Affymetrix GeneChips.
- Ingenuity pathway analysis was employed to identify targeted pathways.
Main Results:
- PPD demonstrated significant inhibition of cancer cell growth by inducing G1 cell cycle arrest and apoptosis.
- Microarray analysis revealed altered expression of 76 genes (52 upregulated, 24 downregulated).
- PPD regulates the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, involving interactions between p53 and DR4/DR5.
Conclusions:
- PPD is a potent inhibitor of colon cancer growth.
- The TRAIL pathway, modulated by p53 and DR4/DR5 interactions, is crucial for PPD's anticancer activity.
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