Targeting the Wingless Signaling Pathway with Natural Compounds as Chemopreventive or Chemotherapeutic Agents

Marie-Helene      Teiten; Francois      Gaascht; Mario      Dicato; Marc      Diederich

Abstract

The aberrant activation of the wingless (Wnt) signaling pathway is a key element involved in carcinogenesis as Wnt regulates a variety of cellular processes including proliferation, differentiation, survival, apoptosis and cell motility. Upon Wnt receptor activation, the canonical “Wnt/beta-catenin” as well as the non canonical “Wnt/planar cell polarity, Wnt/Ca²⁺” pathways are activated. This offers multiple possibilities to target the aberrant regulation of this signaling pathway in order to counteract cancer proliferation. During the last decade, natural compounds from both marine and terrestrial origins were tested for their potential to modulate the expression of specific genes related to the Wnt signaling cascade but also for their anti-carcinogenic properties. It appears that phenolic compounds (e.g., caffeic acid phenethyl ester, curcumin and derivatives, green, white and black tea, resveratrol, quercetin, isoflavone, fisetin, and isoflavone) as well as other small molecules were able to inhibit the Wnt signaling through the modulation of beta-catenin expression, transcriptional activity and of the subsequent expression of Wnt target genes. Altogether, these findings underline the fact that Wnt signaling could be considered as a promising target for innovative strategies for cancer treatment and prevention.

Keywords: Beta-catenin, cancer, chemoprevention, chemotherapy, natural compounds, wingless signaling pathway, carcinogenesis, Wnt/beta-catenin, counteract cancer proliferation, phenolic compounds, esveratrol, quercetin, cancer treatment and prevention