Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Zhu, Wenbin; Xiao, Ni; Liu, Xing‐Jie

doi:10.3892/ol.2017.7307

Cited by 30 publications

(25 citation statements)

References 34 publications

(51 reference statements)

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“…TF have been shown to exhibit antitumor activity various human cancer cells (26). A previous study has demonstrated that TF significantly inhibited tumor growth and induced the apoptosis of prostate cancer cells via the PI3K/Akt/phosphatase and tensin homolog signaling pathway, which provided a theoretical basis for the investigation of the anti-cancer effects of TF (27)(28)(29). Furthermore, TF reduced the proliferation and promoted apoptosis of the human breast cancer cell line MCF-7, by selectively reducing BCL2 and nuclear factor-κB expression and increasing the expression of caspase-3 and 9, suggesting that TF inhibited cellular proliferation by activating the mitochondria-dependent apoptotic pathway (30).…”

Section: Discussionmentioning

confidence: 99%

Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway

Han

Fang

et al. 2020

Oncol Lett

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The aim of the present study was to explore the anti-cancer effects of total flavonoids (TF) on lung cancer and to investigate the underlying mechanism. The inhibitory effect of TF on the proliferation of A549 cells in vitro was measured using an MTT assay. The apoptotic rate of TF-treated A549 cells was analyzed using flow cytometry and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling. Migration and invasion assays were performed to investigate the anti-migration effect of TF on A549 cells. Reverse-transcription quantitative PCR was used to analyze BCL2-like 2, BCL2, Bax, Bad, cyclooxygenase 2 (COX-2), Wnt and β-catenin mRNA expression levels in A549 cells. The in vivo anti-cancer effect of TF was investigated in a subcutaneous xenograft model of lung cancer in BALB/c nude mice. The results obtained in the present study revealed that TF exerted a significant inhibitory effect on the proliferation of A549 cells in a dose-dependent manner (P<0.01). TF induced apoptosis of A549 cells, which exhibited increased and decreased expression of pro-and anti-apoptotic genes, respectively. Furthermore, TF had a significant inhibitory effect on the migration and invasion of A549 cells (P<0.01). The mRNA expression levels of COX-2, Wnt and β-catenin were significantly downregulated in TF-treated A549 cells compared with controls. Additionally, treatment with TF inhibited tumor growth in mice, with a tumor inhibition rate of 64.07% compared with the controls. TF exhibited significant tumor inhibitory effects in vivo by promoting the apoptosis of tumor cells. In conclusion, the results suggested that TF may regulate lung cancer growth via the COX-2-Wnt/β-catenin signaling pathway. TF may serve as a novel anti-cancer agent for the treatment of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway

Han

Fang

et al. 2020

Oncol Lett

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“…LINC01296 knockdown inhibited the proliferation, migration and invasion of 22Rv1 and LNCaP cell. The PI3K/Akt/mTOR signaling pathway, one of the three main signaling pathways, plays an important role in the development and progression of PC [ 4 , 38 ]. Interestingly, LINC01296 knockdown significantly reduced the expression levels of phosphorylated PI3k (p-PI3k), phosphorylated Akt (Ser473)(p-Akt) and phosphorylated mTOR (p-mTOR).…”

Section: Introductionmentioning

confidence: 99%

Pathological bases and clinical impact of long noncoding RNAs in prostate cancer: a new budding star

Lin

Cheng

et al. 2018

Mol Cancer

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Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Recent advances in the non-protein coding part of human genome analysis have discovered extensive transcription of large RNA transcripts that lack coding protein function, termed non-coding RNA (ncRNA). It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in diverse diseases are not yet fully understood. Thus, it is anticipated that more efforts should be made to clarify the lncRNA world. Moreover, accumulating evidence has demonstrated that many lncRNAs are dysregulated in prostate cancer (PC) and closely related to tumorigenesis, metastasis, and prognosis or diagnosis. In this review, we will briefly outline the regulation and functional role of lncRNAs in PC. Finally, we discussed the potential of lncRNAs as prospective novel targets in PC treatment and biomarkers for PC diagnosis.

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“…Moreover, tangeretin inhibits EMT in PC-3 prostate cancer cells by downregulating the PI3K/Akt/mTOR pathway (48). However, the effects of tangeretin on PI3K signaling and of PIK3CA mutation on metastatic breast cancer cells need to be clari ed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Study Reveals Tangeretin Targets and Molecular Mechanisms Against Metastatic Breast Cancer

Hermawan

Putri

Hanif

et al. 2020

Preprint

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Background: Agents that target metastasis are important to improve treatment efficacy in patients with breast cancer. Tangeretin, a citrus flavonoid, exhibits antimetastatic effects on breast cancer cells, but its molecular mechanism remains unclear.Results: Tangeretin targets were retrieved from PubChem, whereas metastatic breast cancer regulatory genes were downloaded from PubMed. In total, 58 genes were identified as potential therapeutic target genes of tangeretin (PTs). Gene ontology analysis with Webgestalt showed that the PTs participate in the biological process of stimulus response, are the cellular components of the nucleus and the membrane, and play molecular roles in enzyme regulation. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the PTs regulate the PI3K/Akt pathway. Genetic alterations for each target gene were MTOR (3%), NOTCH1 (4%), TP53 (42%), MMP9 (4%), NFKB1 (3%), PIK3CA (32%), PTGS2 (15%), and RELA (5%). The Kaplan–Meier plot displayed that patients with low mRNA expression levels of MTOR, TP53, MMP9, NFKB1, PTGS2, and RELA and high expression of PIK3CA had a significantly better prognosis than their counterparts. Further validation of gene expression by using GEPIA revealed that the mRNA expression of MMP9 was significantly lower in breast cancer tissues than in normal tissues, whereas the mRNA expression of PTGS2 showed the opposite. Analysis with ONCOMINE demonstrated that the mRNA expression levels of MMP9 and NFKB1 were significantly higher in metastatic breast cancer cells than in normal tissues. The results of molecular docking analyses revealed the advantage of tangeretin as an inhibitor of PIK3CA, MMP9, PTGS2, and IKK.Conclusion: Tangeretin inhibits metastasis in breast cancer cells by targeting TP53, PTGS2, MMP9, and PIK3CA and regulating the PI3K/Akt signaling pathway. Further investigation is needed to validate the results of this study.

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Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Cited by 30 publications

References 34 publications

Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway

Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway

Pathological bases and clinical impact of long noncoding RNAs in prostate cancer: a new budding star

Integrative Bioinformatics Study Reveals Tangeretin Targets and Molecular Mechanisms Against Metastatic Breast Cancer

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