Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts.
- Koval A Department of Pharmacology and Toxicology, University of Lausanne, Switzerland.
- Pieme CA Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; Department of Biochemistry and Physiological Sciences, University of Yaounde I, Cameroon.
- Queiroz EF School of Pharmaceutical Sciences, University of Geneva, Switzerland.
- Ragusa S (d)Department of Oncology, Ludwig Cancer Research, Lausanne Branch, and Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland.
- Ahmed K Department of Pharmacology and Toxicology, University of Lausanne, Switzerland.
- Blagodatski A Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
- Wolfender JL School of Pharmaceutical Sciences, University of Geneva, Switzerland.
- Petrova TV (d)Department of Oncology, Ludwig Cancer Research, Lausanne Branch, and Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, Switzerland.
- Katanaev VL Department of Pharmacology and Toxicology, University of Lausanne, Switzerland; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia. Electronic address: vladimir.katanaev@unil.ch.
- 2018-08-12
Published in:
- Cancer letters. - 2018
Colon cancer
Natural products
Polyphenols
Tannins
Triple-negative breast cancer
Wnt signaling
Cameroon
Cell Line, Tumor
Cell Proliferation
Cell Survival
Colonic Neoplasms
Gene Expression Regulation, Neoplastic
Humans
Plant Extracts
Syzygium
Tannins
Triple Negative Breast Neoplasms
Wnt Proteins
Wnt Signaling Pathway
Wnt3A Protein
English
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1016/j.canlet.2018.08.003
- PMID 30098400
- Persistent URL
- https://sonar.ch/global/documents/232777
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