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

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.

The Effect of Purified Flavonoids (Tannins) of Tilia Flower on the Proliferation and the Migration Activity of Cancer Cells

“…This result was in agreement with a previous study used CTs from black beans that showed anti-proliferation activity against several cancer cell types (Bawadi et al, 2005). Tannin extracts might also interfere with oncogenic pathways such as Wnt as a recent study showed the inhibitory effect of tannins on the Wnt signaling pathway and cancer cell proliferation (Koval et al, 2018).…”

The Natural Products and Extracts: Anti‐Triple‐Negative Breast Cancer in Vitro

“…Indeed, S. guineense extract could suppress Wnt3a-related β-catenin stabilization and transcript response. [82] The ethanol extract of Cyperus rotundus L. (EECR) inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells in a dose-dependent manner, and it blocked the cell cycle of G0/G1 phase. EECR could induce apoptosis by promoting the expression of Bax and inhibiting the expression of Bcl-2.…”

Natural products against renin-angiotensin system for antifibrosis therapy

“…XAV939 and clofazimine have been identified as Wnt inhibitors and promising anti-TNBC drugs, but neither of them have yet been used in advanced clinical trials [80,81]. Fortunately, tannins, isolated from Syzygium guineense, directly inactivates the stabilization and transcription of Wnt3a-induced β-catenin expression, which may be pursued for novel therapies [82]. As the most potent anti-cancer carotenoids in saffron, crocin exhibits a more potent anti-metastatic ability on TNBC through downregulating FZD7 mRNA expression and upregulating Ecadherin expression in the Wnt/β-catenin pathway [83].…”