TABLE 1.
Molecular targets to reduce BCSCs by targeting signaling pathways.
| Molecule | Signaling pathway | Target | Effect | References |
|---|---|---|---|---|
| Anti-Fzd7 (SHH002-hu1) | Wnt signaling | Frizzled-7 | Reduces bevacizumab-induced proliferation, migration, invasion, and epithelial-mesenchymal transition of triple-negative breast cancer cells by blocking CTC self-renewal | Xie et al. (2021) |
| Apatinib | Wnt signaling | RTK inhibitor | It reduces cell viability, migration, invasion, clonogenic capacity, sphere formation capacity and blocks the expression of markers associated with the stem phenotype of breast cancer cell lines | Jiang et al. (2022) |
| CWP232228 | Wnt signaling | β-catenin/TCF | Reduces the clonogenic self-renewal capacity of CTCs. It also prevents the resistance of breast cancer cell lines to conventional chemotherapeutic treatments | Jang et al. (2015a) |
| Diallyl Trisulfide | Wnt signaling | - | It reduces the ability to mammospheres formation, decreases the expression of stem-associated markers, inhibits cell proliferation, and induces apoptosis in breast cancer cell lines | Li et al. (2018a) |
| Diosgenin | Wnt signaling | - | It inhibits cell proliferation and induces apoptosis of CTCs by favoring the expression of the Wnt antagonist sFRP4 from breast cancer cell lines | Bhuvanalakshmi et al. (2017) |
| Hydroxytyrosol | Wnt signaling | - | It reduces the population of CTC CD44+/CD24- and ALDH positive. It decreases epithelial-msenchymal transition, migration and invasion of breast cancer cell lines | Cruz-Lozano et al. (2019) |
| LGK-974 | Wnt signaling | PORCN | It reduces carboplatin resistance and the expression of genes associated with the stem phenotype of breast cancer cell lines | Abreu de Oliveira et al. (2021) |
| Oxymatrine | Wnt signaling | - | Decreases of side population cells in breast cancer cell lines | Zhang et al. (2011) |
| PKF118–310 | Wnt signaling | TCF4 | Reduces the expression of epithelial-mesenchymal transition and stemness markers in combination with the inhibition of SAHA histone deacetylases. In addition, it reduces tumor growth in breast cancer cells | Hallett et al. (2012), Shamsian et al. (2020) |
| Plumbagin | Wnt signaling | - | It inhibits clonogenic capacity and the expression of markers associated with stemness, tumorigenesis, and metastasis of breast cancer cells | Sakunrangsit and Ketchart (2019) |
| Prodigiosin | Wnt signaling | - | Inhibits proliferation, migration, and tumorigenesis in breast cancer cell lines | Wang et al. (2016) |
| Resveratrol | Wnt signaling | - | Decreases CTC in vivo and in vitro of breast cancer cell lines | Fu et al. (2014) |
| Ursolic acid | Wnt signaling | - | It reduces stem characteristics by overexpressing the Wnt inhibitor sFRP4 and suppressing the expression of miR-499a-5p in breast cancer cell lines | Mandal et al. (2021) |
| 6-Methoxymellein | NF-κB signaling | - | It inhibits cell proliferation and migration, reduces the CD44+/CD24- population, decreases the ability to form mammospheres and the expression of markers associated with the stem phenotype of breast cancer cell lines | Liu et al. (2020a) |
| Anthocyanins | NF-κB signaling | - | It inhibits cell proliferation and avoids cell resistance to conventional chemotherapeutic treatments of breast cancer cell lines | Paramanantham et al. (2020) |
| Aspirin | NF-κB signaling | - | It avoids chemoresistance of breast cancer cells by reducing the acquisition of the stemness of these cells | Saha et al. (2016) |
| Disulfiram | NF-κB signaling | - | Reduces stem characteristics and induces paclitaxel-mediated cytotoxicity of breast cancer cell lines | Yip et al. (2011) |
| Eugenol | NF-κB signaling | - | It prevents cisplatin resistance of breast cancer cell lines by blocking the expansion of ALDH-positive CTCs | Islam et al. (2018) |
| Machilin D | NF-κB signaling | - | It inhibits cell migration and invasion, as well as stem characteristics of breast cancer cell lines | Zhen et al. (2020) |
| Nalbuphine | NF-κB signaling | - | It inhibits cell proliferation, several stem characteristics, the epithelial-mesenchymal transition, and tumorigenesis of breast cancer cell lines | Yu et al. (2019) |
| Pterostilbene | NF-κB signaling | - | It inhibits the acquisition of stem cell characteristics and the metastatic potential induced by M2 macrophages of breast cancer cells | Mak et al. (2013) |
| Sulconazole | NF-κB signaling | - | It inhibits proliferation, tumor growth, mammospheres formation and the expression of stem markers of breast cancer cell lines | Choi et al. (2019) |
| Sulforaphane | NF-κB signaling | - | Blocks CTC expansion and sensitizes cells to chemotherapy in breast cancer cells | Burnett et al. (2017) |
| Tanshinone IIA | NF-κB signaling | - | It blocks several stem cell features by inhibiting IL-6/STAT3/NF-kB signaling in breast cancer cells | Lin et al. (2013) |
| Celastrol | Notch signaling | - | Reduces the ability to mammospheres formation and the expression of markers associated with the stemness of triple negative breast cancer cell lines | Ramamoorthy et al. (2021) |
| DAPT | Notch signaling | γ-secretase | Reduces stemness characteristics, the expression of markers associated with stem in vitro, as well as metastasis and tumorigenesis in vivo | McGowan et al. (2011), Farnie et al. (2013) |
| GSIXII | Notch signaling | γ-secretase | It induces apoptosis and reduces the mammosphere-forming capacity of breast cancer cell lines | Séveno et al. (2012) |
| hN1-NRR/Fc (Anti-Notch antiboy) | Notch signaling | Notch | Inhibits tumorigenesis and decreases stemness in vivo and in vitro of breast cancer cell lines | Qiu et al. (2013) |
| LY-411575 | Notch signaling | γ-secretase | Decreases the ability to form mammospheres and the ability to form colonies on soft agar of breast cancer cell lines | Grudzien et al. (2010) |
| MRK-003 | Notch signaling | γ-secretase | It decreases the ability to form mammospheres, the ability to form colonies on soft agar, and tumorigenesis in breast cancer cells | Grudzien et al. (2010), Kondratyev et al. (2012) |
| Notch-1-Fc | Notch signaling | Notch | Decreases proliferation and the ability to form mammospheres of breast cancer cell lines | Grudzien et al. (2010) |
| Psoralidin | Notch signaling | - | Reduces the population of ALDH-positive CTCs, epithelial-mesenchymal transition, and tumorigenesis of breast cancer cell lines | Pal et al. (2017) |
| Triptolide | Notch signaling | - | Reduces the expression of stemness-associated markers, and formation of mammospheres in triple-negative breast cancer cell lines | Ramamoorthy et al. (2021) |
| Z-Leu-Leu-Nle-CHO | Notch signaling | γ-secretase | Decreases the ability to form colonies on soft agar and mammospheres of breast cancer cell lines | Grudzien et al. (2010) |
| Curcumin | Wnt and Hedgehog signaling | - | It decreases the ability to form mammospheres, the expression of markers associated with stemness, and induces CTC apoptosis of breast cancer cell lines | Li et al. (2018b) |
| GANT61 | Hedgehog signaling | Gli | It decreases cell proliferation, increases apoptosis and decreases the ability to form mammospheres of ER + breast cancer cell lines | Kurebayashi et al. (2017) |
| Genistein | Hedgehog signaling | - | Decreases cell proliferation, CTC ratio and tumorigenicity of breast cancer cell lines | Fan et al. (2013) |
| HPI-1 | Hedgehog signaling | Gli | Decreases proliferation, migration and stemming of breast cancer cell lines | Jeng et al. (2018) |
| Huaier aqueous extract | Hedgehog signaling | - | It decreases cell viability, the ability to form mammospheres and the CD44+ CD24− CTC population of breast cancer cell lines | Wang et al. (2014b) |
| Metformin | Hedgehog signaling | - | Decreases proliferation, migration, metastasis, tumorigenesis and stemming of breast cancer cell lines | Fan et al. (2015) |
| Nitidine Chloride | Hedgehog signaling | - | It decreases cell viability, cell migration, the expression of epithelial-mesenchymal transition genes and the stemness of breast cancer cell lines | Sun et al. (2016) |
| Salinomycin | Hedgehog signaling | - | Decreases cell proliferation, increases apoptosis, decreases migration, and stemness of breast cancer cell lines | Lu et al. (2015) |
| Thiostrepton | Hedgehog signaling | - | Reduces proliferation, self-renewal, and the expression of markers associated with stemness of breast cancer cells | Yang et al. (2016) |
| Physalin A | Hedgehog and YAP/TAZ signaling | It inhibits cell proliferation, the ability to form mammospheres, the expression of markers associated with stemness and the CD44+ CD24− and ALDH-positive CTC population of breast cancer cell lines | Ko et al. (2021) | |
| Chlorpromazine | YAP/TAZ signaling | - | Reduces the ability to mammospheres forming, the expression of markers associated with the stem phenotype and the resistance to chemotherapies of breast cancer cell lines | Yang et al. (2019) |
| Ciclesonide | YAP/TAZ signaling | - | It reduces proliferation, tumorigenesis, mammospheres formation capacity, and stemness markers through the glucocorticoid receptor-dependent YAP signal | Kim et al. (2020) |
| Quinacrine | YAP/TAZ signaling | - | Reduces the expression levels of molecules of the YAP/TAZ pathway in CTC of breast cell lines | Darbankhales et al. (2020) |
| Verteporfin | YAP/TAZ signaling | YAP | It decreases the expression of genes associated with the stem phenotype, cell viability, and resistance to chemotherapy in breast cancer cell lines | Guimei et al. (2020) |
| EW-7197 | TGF-β signaling | ALK5 | Decreases tumor growth in vivo, epithelial-mesenchymal transition, and paclitaxel-induced truncal characteristics in breast cancer | Park et al. (2015) |
| LY2157299 | TGF-β signaling | TβRI | It reduces tumorigenesis by inhibiting stem characteristics of breast cancer cell lines | Bhola et al. (2013) |
| Vactosertib | TGF-β signaling | TβRI | It blocks the increase in cell migration, epithelial-mesenchymal transition, stemness, and the increase in reactive oxygen species caused by radiation. In addition, it inhibits lung metastasis in vivo from breast cancer cell lines | Choi et al. (2022) |
| ZL170 | TGF-β signaling | TGFß/BMP | Reduces migration, invasion, proliferation, epithelial-mesenchymal transition, and stem characteristics in vitro. In addition, it reduces tumorigenesis and metastasis to bone and lung in vivo of breast cancer cells | Di et al. (2019) |