Histone deacetylase inhibitors suppress thymidylate synthase gene expression and synergize with the fluoropyrimidines in colon cancer cells

2009 ◽  
Vol 125 (2) ◽  
pp. 463-473 ◽  
Author(s):  
William Fazzone ◽  
Peter M. Wilson ◽  
Melissa J. LaBonte ◽  
Heinz-Josef Lenz ◽  
Robert D. Ladner
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Thymidylate Synthase ◽  
Histone Deacetylase Inhibitors ◽  
Colon Cancer Cells

scholarly journals Histone Deacetylase Inhibitors Sensitize TRAIL-Induced Apoptosis in Colon Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 645 ◽  
Author(s):  
Baojie Zhang ◽  
Bin Liu ◽  
Deng Chen ◽  
Rita Setroikromo ◽  
Hidde J. Haisma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Combined Treatment ◽  
Specific Inhibitor ◽  
Normal Mucosa ◽  
Class I ◽  
Colon Cancer Cells ◽  
Induced Apoptosis

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as a promising anti-cancer therapeutic. However, many cancers have been found to be or to become inherently resistant to TRAIL. A combination of epigenetic modifiers, such as histone deacetylase inhibitors (HDACi’s), with TRAIL was effective to overcome TRAIL resistance in some cancers. Broad spectrum HDACi’s, however, show considerable toxicity constraining clinical use. Since overexpression of class I histone deacetylase (HDAC) has been found in colon tumors relative to normal mucosa, we have focused on small spectrum HDACi’s. We have now tested agonistic receptor-specific TRAIL variants rhTRAIL 4C7 and DHER in combination with several class I specific HDACi’s on TRAIL-resistant colon cancer cells DLD-1 and WiDr. Our data show that TRAIL-mediated apoptosis is largely improved in WiDr cells by pre-incubation with Entinostat-a HDAC1, 2, and 3 inhibitor- and in DLD-1 cells by RGFP966-a HDAC3-specific inhibitor- or PCI34051-a HDAC8-specific inhibitor. We are the first to report that using RGFP966 or PCI34051 in combination with rhTRAIL 4C7 or DHER represents an effective cancer therapy. The intricate relation of HDACs and TRAIL-induced apoptosis was confirmed in cells by knockdown of HDAC1, 2, or 3 gene expression, which showed more early apoptotic cells upon adding rhTRAIL 4C7 or DHER. We observed that RGFP966 and PCI34051 increased DR4 expression after incubation on DLD-1 cells, while RGFP966 induced more DR5 expression on WiDr cells, indicating a different role for DR4 or DR5 in these combinations. At last, we show that combined treatment of RGFP966 with TRAIL variants (rhTRAIL 4C7/DHER) increases apoptosis on 3D tumor spheroid models.

scholarly journals Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrea Halaburková ◽  
Rastislav Jendželovský ◽  
Ján Kovaľ ◽  
Zdenko Herceg ◽  
Peter Fedoročko ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Epigenetic Regulation ◽  
Histone Deacetylase Inhibitors ◽  
Colon Cancer Cells

Down-regulation of thymidylate synthase expression and its steady-state mRNA by oxaliplatin in colon cancer cells

2004 ◽  
Vol 15 (4) ◽  
pp. 371-376 ◽  
Author(s):  
Kun-Huei Yeh ◽  
Ann-Lii Cheng ◽  
Joeu-Pei Wan ◽  
Chien-Shing Lin ◽  
Chih-Chun Liu
Keyword(s):  
Colon Cancer ◽  
Steady State ◽  
Cancer Cells ◽  
Thymidylate Synthase ◽  
Colon Cancer Cells ◽  
Down Regulation
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