Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/61401
Title: Mechanistic study of the anti-cancer effect of gynostemma pentaphyllum saponins in the ApcMin/+ mouse model
Authors: Tai, WCS
Wong, WY
Lee, MML
Chan, BD
Lu, C
Hsiao, WLW
Keywords: Animal proteomics
ApcMin/+ mice
Colorectal cancer
Gynostemma pentaphyllum
Saponins
Issue Date: 2016
Publisher: Wiley-VCH
Source: Proteomics, 2016, v. 16, no. 10, p. 1557-1569 How to cite?
Journal: Proteomics 
Abstract: Gynostemma pentaphyllum saponins (GpS) have been shown to have anti-cancer activity. However, the underlying mechanisms remain unclear. In this study, we used the ApcMin/+ colorectal cancer (CRC) mouse model to investigate the anti-cancer effect of GpS and we demonstrated that GpS treatment could significantly reduce the number and size of intestinal polyps in ApcMin/+ mice. In order to identify the potential targets and mechanisms involved, a comparative proteomics analysis was performed and 40 differentially expressed proteins after GpS treatment were identified. Bioinformatics analyses suggested a majority of these proteins were involved in processes related to cellular redox homeostasis, and predicted Raf-1 as a potential target of GpS. The upregulation of two proteins known to be involved in redox homeostasis, peroxiredoxin-1 (Prdx1) and peroxiredoxin-2 (Prdx2), and the downregulation of Raf-1 were validated using Western blot analysis. After further investigation of the associated signaling networks, we postulated that the anti-cancer effect of GpS was mediated through the upregulation of Prdx1 and Prdx2, suppression of Ras, RAF/MEK/ERK/STAT, PI3K/AKT/mTOR signaling and modulation of JNK/p38 MAPK signaling. We also examined the potential combinatorial effect of GpS with the chemotherapeutic 5-fluorouracil (5-FU) and found that GpS could enhance the anti-cancer efficacy of 5-FU, further suppressing the number of polyps in ApcMin/+ mice. Our findings highlight the potential of GpS as an anti-cancer agent, the potential mechanisms of its anti-cancer activities, and its effect as an adjuvant of 5-FU in the chemotherapy of CRC.
URI: http://hdl.handle.net/10397/61401
ISSN: 1615-9853
EISSN: 1615-9861
DOI: 10.1002/pmic.201500293
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