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

Autor: Jean-Luc Wolfender, Constant Anatole Pieme, Vladimir L. Katanaev, Tatiana V. Petrova, Artem Blagodatski, Emerson Ferreira Queiroz, Kamal Ahmed, Alexey Koval, Simone Ragusa
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
Colorectal cancer
Syzygium
Triple Negative Breast Neoplasms
Syzygium/chemistry
Syzygium guineense
Wnt Signaling Pathway/drug effects/genetics
Neoplastic/drug effects
Cameroon
Wnt Signaling Pathway
Triple-negative breast cancer
2. Zero hunger
ddc:615
Tumor
Wnt signaling pathway
Cell Proliferation/drug effects/genetics
3. Good health
Gene Expression Regulation
Neoplastic
Tannins/pharmacology
Oncology
Colonic Neoplasms
medicine.symptom
Cell Survival
Wnt3A Protein/genetics/metabolism
Biology
Colonic Neoplasms/genetics/metabolism/pathology
Cell Line
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Wnt3A Protein
medicine
Humans
Triple Negative Breast Neoplasms/genetics/metabolism/pathology
Cell Proliferation
Plant Extracts
Cell Survival/drug effects/genetics
Plant Extracts/pharmacology
medicine.disease
biology.organism_classification
Wnt Proteins
030104 developmental biology
Gene Expression Regulation
Mechanism of action
Cancer cell
Cancer research
Tannins
Wnt Proteins/genetics/metabolism
WNT3A
Zdroj: Cancer Letters, Vol. 435 (2018) pp. 110-120
ISSN: 0304-3835
Popis: 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.
Databáze: OpenAIRE
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