4.1. Phytomedicines targeting Wnt signaling pathway
Various phytocompounds have proved to eliminate CSCs by modulating Wnt
signaling pathway. It was demonstrated in a study that garlic derivative
organosulfur compound diallyl trisulfide enhanced GSK3-β expression and
decreased β-catenin levels, signifying the suppression of Wnt/β-catenin
pathway in colorectal CSCs (Zhang et al., 2018) . Koenimbin
extracted from leaves of Murraya koenigii (L) Spreng induced
β-catenin at Ser33/37/Thr41 and inhibited MCF7 breast CSCs(Kamalidehghan et al., 2015) . In another study, it has been
shown that ginsenoside-Rb1, the main saponin present in rhizome of
ginseng targets ovarian CSCs by inhibiting Wnt/β-catenin signaling
pathway and EMT. Compound K, a metabolite of ginsenoside-Rb1 was found
to be effective in suppressing tumors in mouse xenografts (50 mg/kg dose
of compound K) (Deng et al., 2017) . Abrus agglutinin, a lectin
extracted from seeds of Abrus precatorius was shown to induce
apoptosis, inhibit EMT and interfere with Wnt/β-catenin signaling in
oral squamous carcinoma cells and suppressed the tumor with 50 μg/kg
dose of purified Abrus agglutinin in xenografted nude mice(Sinha et al., 2017, 2019) . 60 mg/kg dose of Cruciferous
sulforaphane inhibited nasopharyngeal CSCs in nude mice xenografts
through DNA methyltransferase 1/Wnt inhibitory factor 1 axis(Chen et al., 2019) . Likewise, it caused suppression of miR-19
and Wnt/β-catenin pathway and inhibited lung CSCs (Zhu et al.,
2017) . Rhodiola crenulata root extract and chelerythrine
chloride were shown to reduce β-catenin levels and thus suppress CSC
characteristics (Bassa et al., 2016; Heng & Cheah, 2020) .
Sanguinarine, obtained from TCM celandine and water extract ofGynura divaricata also downregulated Wnt pathway (J. Yang
et al., 2016; Yen et al., 2018) . Gomisin M2, an active component of a
Chinese medicine Baizuan, exhibited apoptotic effect on breast CSCs and
suppressed tumor with 10 μM dose of Gomisin M2 in zebrafish xenografts(Y. Yang et al., 2019) . Evodiamine, a constituent ofEvodiae, exhibited anti-tumor activity against gastric and colon
CSCs by dysregulation of Wnt pathway (Kim et al., 2019; Wen et
al., 2015) .