| Synergistic effect of histone deacetylase inhibitors FK228 and m-carboxycinnamic acid bis-hydroxamide with proteasome inhibitors PSI and PS-341 against gastrointestinal adenocarcinoma cells. | |
| | |
MedLine Citation:
|
PMID: 15173094 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: We investigated whether the histone deacetylase inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and a bicyclic depsipeptide, FK228, can enhance the anticancer effect of the proteasome inhibitors PSI and PS-341 in gastrointestinal carcinoma cells. EXPERIMENTAL DESIGN: The anticancer effect of CBHA or FK228 and PSI or PS-341 was evaluated by cell death, caspase-3 activity, externalization of phosphatidylserine and DNA fragmentation, and colony formation assay. Expression of apoptosis-related molecules and cell cycle regulatory molecules, as well as phosphorylation of p38 were investigated by immunoblots. Generation of reactive oxygen species (ROS) was detected by intracellular oxidation of 5- (and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate. RESULTS: CBHA or FK228 plus PSI or PS-341 synergistically induced apoptosis in human colonic DLD-1 and gastric MKN45 carcinoma cell lines. CBHA or FK228, but not 5-fluorouracil, plus PS-341 strongly decreased plating efficiency of DLD-1 cells. FK228 elicited ROS generation, and the free radical scavenger l-N-acetylcysteine inhibited the synergistic anticancer effect of combined therapy. In addition, l-N-acetylcysteine inhibited the combined therapy-mediated elevation of a proapoptotic BH3-only protein Bim expression, phosphorylation of H2AX, and accumulation of 8-hydroxydeoxyguanosine. CONCLUSIONS: FK228 or CBHA and PSI or PS-341 synergistically induce apoptosis in DLD-1 and MKN45 cells depending on ROS-mediated signals. Our data suggest that a combination of FK228 or CBHA with PSI or PS-341 may be a valuable therapy against gastrointestinal adenocarcinoma cells. |
| | |
Authors:
|
Masaaki Adachi; YuBin Zhang; Xudong Zhao; Takae Minami; Rina Kawamura; Yuji Hinoda; Kohzoh Imai |
Related Documents
:
|
18473264 - Nox-generated ros modulate glucose uptake in a leukaemic cell line. 20580704 - The natural antioxidant alpha-lipoic acid induces p27(kip1)-dependent cell cycle arrest... 20946354 - Anthrolysin o and fermentation products mediate the toxicity of bacillus anthracis to l... 15040354 - Cytotoxic effects of b lymphocytes mediated by reactive oxygen species. 2658994 - The binding activities of proteins that bind ap4a, an alarmone, are stimulated in the p... 4506784 - Regeneration of cation-transport capacity in hela cell membranes after specific blockad... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 10 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2004 Jun |
Date Detail:
|
Created Date: 2004-06-02 Completed Date: 2004-12-27 Revised Date: 2008-06-02 |
Medline Journal Info:
|
Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
|
Languages: eng Pagination: 3853-62 Citation Subset: IM |
Affiliation:
|
Graduate School of Medicine and First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. adachi@sapmed.ac.jp |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenocarcinoma
/
drug therapy* Annexin A5 / pharmacology Antibiotics, Antineoplastic / pharmacology Antineoplastic Combined Chemotherapy Protocols / pharmacology* Apoptosis Blotting, Western Boronic Acids / pharmacology* Caspase 3 Caspases / metabolism Cell Line, Tumor Cinnamates / pharmacology* Colonic Neoplasms / metabolism DNA Fragmentation Depsipeptides / pharmacology* Dose-Response Relationship, Drug Drug Synergism Enzyme Inhibitors / pharmacology* Free Radicals Gastrointestinal Neoplasms / drug therapy* Histones / metabolism Humans Microscopy, Confocal Oligopeptides / pharmacology* Oxygen / metabolism Phosphorylation Proteasome Endopeptidase Complex / antagonists & inhibitors* Pyrazines / pharmacology* Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors |
| Chemical | |
Reg. No./Substance:
|
0/Annexin A5; 0/Antibiotics, Antineoplastic; 0/Boronic Acids; 0/Cinnamates; 0/Depsipeptides; 0/Enzyme Inhibitors; 0/Free Radicals; 0/Histones; 0/Oligopeptides; 0/Pyrazines; 0/Reactive Oxygen Species; 0/benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; 0/bortezomib; 0/carboxycinnamic acid bishydroxamide; 128517-07-7/romidepsin; 7782-44-7/Oxygen; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the prote...
Next Document: Noninvasive measurements of capecitabine metabolism in bladder tumors overexpressing thymidine phosp...