Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics

Pandey, Pratibha; Khan, Fahad; Seifeldin, Sara A.; Alshaghdali, Khalid; Siddiqui, Samra; Abdelwadoud, Mohamed Elfatih; Vyas, M. D.; Mazumder, Avijit; Saeed, Amir

doi:10.3390/nu15092088

Cited by 8 publications

(7 citation statements)

References 167 publications

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“…The activation of Wnt/β-catenin signaling pathway can promote malignant phenotype of cancer ( 34 , 35 ). The Wnt/β-catenin signaling pathway is involved in regulating the effect of drugs derived from natural products ( 36 , 37 ). To determine whether sinensetin had anticancer effects in breast cancer cell via inhibiting the Wnt/β-catenin signaling pathway, we performed Western blotting to detect the expression of related proteins in MCF7 and MDA-MB-231 cells exposed to sinensetin.…”

Section: Resultsmentioning

confidence: 99%

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

Zhu,

Meng,

Wei

et al. 2024

Transl Cancer Res

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Background Although there are many treatments for breast cancer, such as surgery, radiotherapy, chemotherapy, estrogen receptor antagonists, immune checkpoint inhibitors and so on. However, safer and more effective therapeutic drugs for breast cancer are needed. Sinensetin, a safer therapeutic drugs, come from citrus species and medicinal plants used in traditional medicine, while its role and underlying mechanism in breast cancer remain unclear. Our study aimed to investigate the role and mechanism of sinensetin in breast cancer. Methods Cell Counting Kit-8 (CCK-8) was used to determine the safe concentration of sinensetin in MCF-10A, MCF7 and MDA-MB-231 cells; 120 μM sinensetin was used in subsequent experiments. Real time polymerase chain reaction (RT-PCR), Western blotting, Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay, Transwell invasion assay and Clone formation assay were used in this study to determine cell viability, mRNA expression, protein levels, apoptosis, proliferation, invasion and so on. Results Herein, our results showed that 120 μM sinensetin suppressed the cell viability and promoted apoptosis of MCF7 and MDA-MB-231 cells. Treatment with 120 µM sinensetin for 24 h showed no significant toxicity to normal mammary cells; 120 μM sinensetin decreased cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), and downregulated β-catenin, lymphatic enhancing factor 1 (LEF1), T-cell factor (TCF) 1/TCF7, and TCF3/TCF7L1 expression in MCF7 and MDA-MB-231 cells. The Wnt agonist SKL2001 reversed the inhibitory effect of sinensetin on cell survival, metastasis, and EMT. Sinensetin-induced downregulation of β-catenin, LEF1, and TCF1/TCF7 expression were upregulated by SKL2001 in MCF7 and MDA-MB-231 cells. Conclusions In summary, sinensetin suppressed the metastasis of breast cancer cell via inhibition of Wnt/β-catenin pathway and there were no adverse effects on normal breast cells. Our study confirmed the role of sinensetin in breast cancer cells and provided a better understanding of the underlying mechanism.

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Section: Resultsmentioning

confidence: 99%

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

Zhu,

Meng,

Wei

et al. 2024

Transl Cancer Res

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“…It is typically inhibited during adulthood but can be reactivated during organ injury and regeneration ( 36 ). The abnormal activation of this signaling pathway is closely related to the increase of tumor incidence, malignant progression, poor prognosis, and even the increase of related mortality ( 37 , 38 ). The Wnt-β-catenin pathway consists of four components: extracellular signaling segment, membrane segment, cytoplasmic segment, and nuclear segment.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study

Jia,

Chen,

Kang

et al. 2024

Transl Androl Urol

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Background Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS1 1 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [β-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in β-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal ...

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“…WNT/β-CATENIN signaling is essential for organogenesis during embryonic development; however, the alteration of adult cells leads to cancer formation. WNT signaling and β-CATENIN play important roles in the various oncogenic processes that give rise to different human malignancies, including CaP [34,35]. WNT/β-CATENIN signaling mediates upsurges in receptor Tyrosine kinase-like orphan receptor 1 (ROR1), increasing noncanonical responses to Wnt5a, which plays an important role in prostate stem cell generation during early development and might be reactivated in the CaP microenvironment.…”

Section: Wnt/β-catenin Signaling Pathwaysmentioning

confidence: 99%

Molecular Insight into Prostate Cancer: Preventive Role of Selective Bioactive Molecules

Jameel,

Fatma,

Nadtochii

et al. 2023

Life

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Prostate cancer (CaP) is one of the most prevalent male malignancies, accounting for a considerable number of annual mortalities. However, the prompt identification of early-stage CaP often faces delays due to diverse factors, including socioeconomic inequalities. The androgen receptor (AR), in conjunction with various other signaling pathways, exerts a central influence on the genesis, progression, and metastasis of CaP, with androgen deprivation therapy (ADT) serving as the primary therapeutic strategy. Therapeutic modalities encompassing surgery, chemotherapy, hormonal intervention, and radiotherapy have been formulated for addressing early and metastatic CaP. Nonetheless, the heterogeneous tumor microenvironment frequently triggers the activation of signaling pathways, culminating in the emergence of chemoresistance, an aspect to which cancer stem cells (CSCs) notably contribute. Phytochemicals emerge as reservoirs of bioactive agents conferring manifold advantages against human morbidity. Several of these phytochemicals demonstrate potential chemoprotective and chemosensitizing properties against CaP, with selectivity exhibited towards malignant cells while sparing their normal counterparts. In this context, the present review aims to elucidate the intricate molecular underpinnings associated with metastatic CaP development and the acquisition of chemoresistance. Moreover, the contributions of phytochemicals to ameliorating CaP initiation, progression, and chemoresistance are also discussed.

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Targeting Wnt/β-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics

Cited by 8 publications

References 167 publications

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

Sinensetin suppresses breast cancer cell progression via Wnt/β-catenin pathway inhibition

Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study

Molecular Insight into Prostate Cancer: Preventive Role of Selective Bioactive Molecules

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