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Scientific article
Open access
English

Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts

Published inCancer Letters, vol. 435, p. 110-120
Publication date2018
Abstract

Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. Extracts from "fruit rouge", Syzygium guineense Wall. (Myrtaceae), demonstrated a strong activity against these cancer cells, as well as CC organoids. We found TNBC cells to significantly upregulate expression of Wnt3a, and the effects of S. guineense extracts on TNBC cell proliferation correlated with inhibition of the Wnt3a-induced β-catenin stabilization and transcriptional response. HPLC analysis revealed that the active components belong to tannins. We found a direct destabilizing effect of S. guineense extract on Wnt3a and other Wnt proteins, identifying a novel mechanism of action of tannins on the Wnt signaling pathway and cancer cell proliferation. Being edible, this African plant may have an important cancer-preventive nutritional value.

Keywords
  • Cameroon
  • Cell Line
  • Tumor
  • Cell Proliferation/drug effects/genetics
  • Cell Survival/drug effects/genetics
  • Colonic Neoplasms/genetics/metabolism/pathology
  • Gene Expression Regulation
  • Neoplastic/drug effects
  • Humans
  • Plant Extracts/pharmacology
  • Syzygium/chemistry
  • Tannins/pharmacology
  • Triple Negative Breast Neoplasms/genetics/metabolism/pathology
  • Wnt Proteins/genetics/metabolism
  • Wnt Signaling Pathway/drug effects/genetics
  • Wnt3A Protein/genetics/metabolism
Citation (ISO format)
KOVAL, Alexey et al. Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts. In: Cancer Letters, 2018, vol. 435, p. 110–120. doi: 10.1016/j.canlet.2018.08.003
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Article (Accepted version)
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Identifiers
ISSN of the journal0304-3835
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