Vitamin C Protects Against UV Irradiation-Induced Apoptosis Through Reactivating Silenced Tumor Suppressor Genes p21 and p16 in a Tet-Dependent DNA Demethylation Manner in Human Skin Cancer Cells

2014 ◽  
Vol 29 (6) ◽  
pp. 257-264 ◽  
Author(s):  
Jin-ran Lin ◽  
Hai-hong Qin ◽  
Wen-yu Wu ◽  
Shu-juan He ◽  
Jin-hua Xu
Keyword(s):  
Skin Cancer ◽  
Tumor Suppressor ◽  
Vitamin C ◽  
Cancer Cells ◽  
Human Skin ◽  
Uv Irradiation ◽  
Tumor Suppressor Genes ◽  
Dna Demethylation ◽  
Suppressor Genes ◽  
Induced Apoptosis

Up-regulation of tumor suppressor genes might promote the malignant phenotype of cancer cells

2007 ◽  
Vol 69 (6) ◽  
pp. 1379 ◽  
Author(s):  
Liu Hong ◽  
Xiaohua Li ◽  
Haifeng Jin ◽  
Li Yan ◽  
Kaichun Wu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Genes ◽  
Malignant Phenotype ◽  
Suppressor Genes

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

2013 ◽  
Vol 267 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Shi-Wei Huang ◽  
Chun-Ying Wu ◽  
Yen-Ting Wang ◽  
Jun-Kai Kao ◽  
Chi-Chen Lin ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cancer Cells ◽  
Human Skin ◽  
Compound C ◽  
Induced Apoptosis

scholarly journals Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms

2019 ◽  
Vol 12 ◽  
pp. 251686571983901 ◽  
Author(s):  
Shahad A Qadi ◽  
Mohammed A Hassan ◽  
Ryan A Sheikh ◽  
Othman AS Baothman ◽  
Mazin A Zamzami ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cell Line ◽  
Rna Sequencing ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Suppressor Genes

The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 ( UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as RASL11B, RASD1, GNG3, BAD, and BIK. Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.

scholarly journals KMT2D inhibits the growth and metastasis of bladder Cancer cells by maintaining the tumor suppressor genes

2019 ◽  
Vol 115 ◽  
pp. 108924 ◽  
Author(s):  
Peng Sun ◽  
Tong Wu ◽  
Xiaoliang Sun ◽  
Zilian Cui ◽  
Haiyang Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Bladder Cancer Cells

scholarly journals Cancer cell-selective killing polymer/copper combination

2016 ◽  
Vol 4 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Huacheng He ◽  
Diego Altomare ◽  
Ufuk Ozer ◽  
Hanwen Xu ◽  
Kim Creek ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Glutathione Level ◽  
Suppressor Genes

A polymer/copper combination selectively kills cancer cells by targeting their high glutathione level, upregulated oncogenes, and downregulated tumor suppressor genes.

Strategies to Re-Express Epigenetically-Silenced Tumor Suppressor Genes Converge on the Requirement for Inhibition of the Histone Methyltransferase SUV39H1.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3357-3357
Author(s):  
Asha Lakshmikuttyamma ◽  
Stuart Scott ◽  
David P. Sheridan ◽  
John DeCoteau ◽  
Ron Geyer
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Fold Increase ◽  
Dna Demethylation ◽  
Dna Hypermethylation ◽  
Suppressor Genes ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
E Cadherin

Abstract Gene silencing mediated by aberrant promoter DNA hypermethylation represents a key mechanism by which tumor suppressor gene expression is silenced in cancer and it is associated with multiple repressive histone modifications. Histone H3 lysine 9 (H3K9) methylation is a key repressive chromatin modification with important implications for regulating cell proliferation, differentiation, and gene expression. SUV39H1 is a methyltransferase that catalyzes the addition of trimethyl groups to H3K9. SUV39H1 is associated with regions of hypermethylated CpG islands, with repressive complexes, such as RB/E2F, and with DNA-binding proteins involved in leukemogenesis, such as AML1 and PML-RAR, where its H3K9 trimethylation activity promotes heterochromatin formation and gene silencing. We studied the requirement of SUV39H1 in the epigenetic silencing of heavily methylated tumor suppressor genes p15INK4B and E-cadherin in acute myeloid leukemia (AML). Treatment of AML cell lines AML193, KG1a, and Kasumi with the DNA methyltransferase (DNMT) inhibitor 5-Aza-2’-deoxycytidine (5-Aza-dC) induces p15INK4B and E-cadeherin re-expression in association with dramatic decreases in p15INK4B and E-cadherin promoter DNA methylation and marked reductions in the levels of SUV39H1 and H3K9 trimethylation at these promoters. Interestingly, treatment of these cell lines with SUV39H1 shRNA, or the SUV39H1 inhibitor chaetocin, also induces p15INK4B and E-cadherin re-expression and H3K9 demethylation, without affecting promoter DNA methylation. Thus, re-expression of hypermethylated tumor suppressors requires histone H3K9 demethylation, which can be achieved indirectly by decreasing the amount of SUV39H1 associated with the promoter using 5-Aza-dC, or directly by inhibiting SUV39H1 expression or activity without requiring promoter DNA demethylation. Furthermore, we found that SUV39H1 shRNA or chaetocin in combination with 5-Aza-dC acts synergistically to re-express epigenetically silenced p15INK4B and E-cadherin in AML cell lines. Treatment of primary human AML blasts obtained from two patients with combinations of 5-Aza-C and chaetocin also results in synergistic re-expression of p15INK4B and E-cadherin (2–6 fold increase with 5-Aza-C or chaetocin treatment vs. 11–14 fold increase with co-treatment). Our study has important implications for developing novel epigenetic therapies of relevance to AML as it suggests that the re-expression of tumor suppressor genes silenced by aberrant promoter DNA hypermethylation converges on the requirement for SUV39H1 and H3K9 methylation inhibition but not promoter DNA demethylation. Our finding that SUV39H1 inhibition may function synergistically with DNMT inhibitors to enhance gene reactivation and chromatin changes also highlights the needs for developing more inhibitors of histone methyltransferases and for performing detailed drug interaction studies to identify the best drug combinations for optimal epigenetic therapies.

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