Novel activators and inhibitors of the Wnt signaling pathway from medicinal plants

A Blagodatski; V Sova; P Gorovoy; A Usov; V Katanaev

doi:10.1055/s-0034-1394517

Planta Medica, Table of Contents

Novel activators and inhibitors of the Wnt signaling pathway from medicinal plants

A Blagodatski ¹^,², V Sova ², P Gorovoy ³, A Usov ⁴, V Katanaev ¹

¹Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
²Institute of Protein Research, Russian Academy of Sciences, Pushchino, Russia
³Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia
⁴Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia

Abstract

The Wnt signaling pathway plays critical roles in embryonic development and is important in adults [1]. This pathway is necessary for stem cell proliferation and regeneration in various tissues. On the other hand, aberrant activation of the Wnt pathway leads to cancers, most notably in the breast and colon [2]. We performed a search for natural Wnt pathway agonists and inhibitors from plant extracts as candidates for cancer treatment, regeneration medicine and stem-cell based technologies. A group of European and Asian plants used in traditional medicine was selected. The plants were extracted using a special water extraction technology at mild temperature, which, unlike the ethanol extraction method, allows extracting compounds in their natural state. The water extracts were then tested for their possible effect on the Wnt cascade activity using several readouts, namely the Top-Flash luciferase assay and the Top-GFP assay, where the activity of Wnt-dependent luciferase or GFP expression was compared between untreated cells and cells treated with extracts [3]. As a result of these experiments, three plant extracts were shown to influence the Wnt cascade activity. The extract from Jerusalem artichoke (Helianthus tuberosus) inhibited the Wnt-activated reporter and was further confirmed by the beta-catenin stabilization assay, which serves as an independent standard for measuring the Wnt pathway activity. The extract of a Far Eastern plant Ampelopsis japonica also showed a Wnt-inhibiting activity in both GFP and luciferase assays. In opposite, the extract of mare's-tail (Equisetum arvense) showed activation of the reporter activity in the absence of a Wnt ligand. So, we have identified two potential Wnt cascade inhibitors and one potential activator. Fractionation and molecular identification of the active components of these extracts is currently being performed, along with tests on the effects of these extracts on triple-negative breast cancer cells in culture.

Keywords: Wnt signaling, cancer, triple-negative breast cancer, plant extracts

References:

[1] Logan CY, Nusse R: The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004, 20: 781 – 810.

[2] Polakis P: Wnt signaling in cancer. Cold Spring Harb Perspect Biol 2012, 4.

[3] Koval AV, Vlasov P, Shichkova P, Khunderyakova S, Markov Y, Panchenko J, Volodina A, Kondrashov FA, Katanaev VL: Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling. Biochem Pharmacol 2014, 87: 571 – 578.