Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer

Qiu, Wei; Lin, Jun; Zhu, Yichen; Zhang, Jian; Zeng, Liping; Su, Ming; Tian, Ye

doi:10.1159/000464435

Cited by 62 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Chemoresistance, which leads to the failure of chemotherapy, is very common in the therapeutic process [8, 45, 46]. Thus, the development of effective chemotherapies is critical.…”

Section: Discussionmentioning

confidence: 99%

“…DNA hypermethylation is associated with hypoxia and reduces the activity of oxygen-dependent ten-eleven translocation enzymes [6]. Cancer cells from many different human tumours exhibit changes in DNA methylation involving both global hypomethylation and local hypermethylation of CpG-rich gene promoters [7, 8]. Hypermethylation of promoter CpG islands implies an important mutation-independent mechanism for inactivation of tumour suppressor genes by gene silencing in cancer cells [9], which ultimately contributes to oncogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Zhang

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. Conclusion: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.

show abstract

“…Chemoresistance, which leads to the failure of chemotherapy, is very common in the therapeutic process [8, 45, 46]. Thus, the development of effective chemotherapies is critical.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Zhang

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…Qiu et al (2017) demonstrated that treatment with the flavonoid kaempferol did not vary the content of 5-methylcytosine, a biomarker for global DNA methylation, in a bladder cancer xenografts model, but modulated DNA methylation in specific positions. Qiu et al (2017) demonstrated that treatment with the flavonoid kaempferol did not vary the content of 5-methylcytosine, a biomarker for global DNA methylation, in a bladder cancer xenografts model, but modulated DNA methylation in specific positions.…”

Section: Discussionmentioning

confidence: 95%

“…Although there was no change in global methylation levels in wild type TP53 cells, there was DNMT1 downregulation (2.27-and 3.57-fold downregulation for 100 and 150 μM, , which may be contributing to demethylation of tumor suppressor genes. Qiu et al (2017) demonstrated that treatment with the flavonoid kaempferol did not vary the content of 5-methylcytosine, a biomarker for global DNA methylation, in a bladder cancer xenografts model, but modulated DNA methylation in specific positions.…”

Section: Discussionmentioning

confidence: 95%

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

Almeida

Guerra

Assis

et al. 2019

Environ and Mol Mutagen

View full text Add to dashboard Cite

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637‐grade 2 and T24‐grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long‐term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest‐grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740–751, 2019. © 2019 Wiley Periodicals, Inc.

show abstract

“…In this respect, kaempferol, as a chemopreventive agent, has been found to modulate DNA methylation, to suppress the protein levels of DNA methyltransferases (DNMT3B) and to induce 103 differential DNA methylation positions (dDMPs) associated with genes 50 hypermethylated and 53 hypomethylated. Additionally, it induces a premature degradation of DNMT3B by suppressing the protein synthesis with cycloheximide (CHXv) (Qiu et al, ). In a recent investigation, Kashafi and coworkers reported that kaempferol (12–100 μM) induces apoptosis and cell death in HeLa cervical cancer cells in a dose‐dependent fashion.…”

Section: Health Perspectivesmentioning

confidence: 99%

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Imran

Rauf

Shah

et al. 2018

Phytotherapy Research

260

154

View full text Add to dashboard Cite

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

show abstract

Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer

Cited by 62 publications

References 35 publications

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status

Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Contact Info

Product

Resources

About