Mechanistic study of the anti-cancer effect of Gynostemma pentaphyllum saponins in the ApcMin/+mouse model

Chi Shing Tai, Wing Yan Wong, Magnolia Muk Lan Lee, Brandon Dow Chan, Cheng Lu, Wen Luan Wendy Hsiao

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)

Abstract

KGaA, Weinheim. 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.
Original languageEnglish
Pages (from-to)1557-1569
Number of pages13
JournalProteomics
Volume16
Issue number10
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • Animal proteomics
  • Apc mice Min/+
  • Colorectal cancer
  • Gynostemma pentaphyllum
  • Saponins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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