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Nutrients 2015, 7(2), 799-814; doi:10.3390/nu7020799

Protopanaxadiol, an Active Ginseng Metabolite, Significantly Enhances the Effects of Fluorouracil on Colon Cancer

1
Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA
2
Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA
3
Department of Orthopedic Surgery, University of Chicago, Chicago, IL 60637, USA
4
Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, IL 60637, USA
*
Author to whom correspondence should be addressed.
Received: 24 October 2014 / Accepted: 14 January 2015 / Published: 23 January 2015
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Abstract

In this study, we evaluated the effects of protopanaxadiol (PPD), a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU) on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p < 0.01), and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p < 0.01). Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p < 0.01). Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p < 0.05). PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p < 0.01 compared to the 5-FU alone). The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU’s cancer therapeutics. View Full-Text
Keywords: protopanaxadiol; ginseng; metabolite; enteric microbiome; fluorouracil; colorectal cancer; HCT-116 cells; cell proliferation; cell cycle; apoptosis; athymic mice; xenograft protopanaxadiol; ginseng; metabolite; enteric microbiome; fluorouracil; colorectal cancer; HCT-116 cells; cell proliferation; cell cycle; apoptosis; athymic mice; xenograft
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, C.-Z.; Zhang, Z.; Wan, J.-Y.; Zhang, C.-F.; Anderson, S.; He, X.; Yu, C.; He, T.-C.; Qi, L.-W.; Yuan, C.-S. Protopanaxadiol, an Active Ginseng Metabolite, Significantly Enhances the Effects of Fluorouracil on Colon Cancer. Nutrients 2015, 7, 799-814.

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