Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties

Jiménez-Guerrero, Rocío; Belmonte-Fernández, Alejandro; Flores, M. Luz; González-Moreno, Mónica; Pérez-Valderrama, Begoña; Romero, Fráncisco; Japón, Miguel Á.; Sáez, Carmen

doi:10.3390/ijms23010450

Cited by 21 publications

(11 citation statements)

References 41 publications

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“…Several cellular signaling pathways have been demonstrated to be important in the formation and maintenance of CSCs, including the canonical Wnt/β-catenin signaling pathway, Notch-signaling pathway and Hedgehog signaling pathway. 44 The canonical Wnt/β-catenin signaling pathway regulates the degradation/nuclear translocation of β-catenin, which acts as a transcription factor and leads to the cancer cell “gain of self-renewal ability.” 45 - 48 Our data here clearly showed that both Pao and Rau reduced the nuclear β-catenin levels at 24 and 48 hours.…”

Section: Discussionsupporting

confidence: 56%

Extracts of the Medicinal Plants Pao Pereira and Rauwolfia vomitoria Inhibit Ovarian Cancer Stem Cells In Vitro

2022

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Ovarian cancer has an enrichment of cancer stem cells (CSCs) which contribute to the treatment resistant tumor’s high rate of recurrence and metastasis. Here we investigated 2 plant extracts from the medicinal plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) each for their activities against ovarian CSCs. Both Pao and Rau inhibited overall proliferation of human ovarian cancer cell lines with IC50 ranging from 210 to 420 μg/mL and had limited cytotoxicity to normal epithelial cells. Ovarian CSC population was examined using cell surface markers and tumor spheroid formation assays. The results showed that both Pao and Rau treatment significantly reduced the ovarian CSC population. Pao and Rau had similar activities in inhibiting ovarian CSCs, with IC50s of ~120 μg/mL for 24 hours treatment, and ~50 μg/mL for long-term tumor spheroid formation. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. Taken together, data here showed that Pao and Rau both inhibited ovarian cancer stem cells, probably in preference to the bulk of tumor cells. Further mechanistic studies and in vivo investigation validating these findings are warranted, given that inhibition of cancer stem cells holds the promise of comprehensively inhibiting cancer metastasis, drug resistance and recurrence.

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Section: Discussionsupporting

confidence: 56%

Extracts of the Medicinal Plants Pao Pereira and Rauwolfia vomitoria Inhibit Ovarian Cancer Stem Cells In Vitro

2022

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“…Guerrero et al. ( 94 ) reported SOX2 expression to be abnormally upregulated in the resistant HT1197 cell line compared with the 5637 cell line, which was not resistant to paclitaxel.…”

Section: Role Of Sox2 In Bladder Cancer Treatment Resistance and Pote...mentioning

confidence: 99%

Impact of SOX2 function and regulation on therapy resistance in bladder cancer

Chen

et al. 2022

Front. Oncol.

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Bladder cancer (BC) is a malignant disease with high rates of recurrence and mortality. It is mainly classified as non-muscle-invasive BC and muscle-invasive BC (MIBC). Often, MIBC is chemoresistant, which, according to cancer stem cells (CSCs) theory, is linked to the presence of bladder cancer stem cells (BCSCs). Sex-determining region Y- (SRY) Box transcription factor 2 (SOX2), which is a molecular marker of BCSCs, is aberrantly over-expressed in chemoresistant BC cell lines. It is one of the standalone prognostic factors for BC, and it has an inherently significant function in the emergence and progression of the disease. This review first summarizes the role of SRY-related high-mobility group protein Box (SOX) family genes in BC, focusing on the SOX2 and its significance in BC. Second, it discusses the mechanisms relevant to the regulation of SOX2. Finally, it summarizes the signaling pathways related to SOX2 in BC, suggests current issues to be addressed, and proposes potential directions for future research to provide new insights for the treatment of BC.

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“…Based on these results, we moved forward in testing the efficacy of PTX-NCS treatment in vivo in an orthotopic TNBC mice model. A number of studies have evaluated the potential of NCS as an anti-cancer therapy in various cancer types in vivo, including TNBC [ 41 , 42 , 43 , 44 ] and stated the ability of NCS to overcome cancer chemoresistance when combined with PTX [ 45 , 46 , 47 ] and other anti-cancer agents [ 48 , 49 ]. However, the synergistic effect of combined treatment in CSC subpopulations has not yet been clearly elucidated.…”

Section: Discussionmentioning

confidence: 99%

Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide

Cámara-Sánchez

Díaz‐Riascos

García‐Aranda

et al. 2022

IJMS

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Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.

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Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties

Cited by 21 publications

References 41 publications

Extracts of the Medicinal Plants Pao Pereira and Rauwolfia vomitoria Inhibit Ovarian Cancer Stem Cells In Vitro

Extracts of the Medicinal Plants Pao Pereira and Rauwolfia vomitoria Inhibit Ovarian Cancer Stem Cells In Vitro

Impact of SOX2 function and regulation on therapy resistance in bladder cancer

Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide

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