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Tytuł pozycji:

Structure-activity relationship of butyrate analogues on apoptosis, proliferation and histone deacetylase activity in HCT-116 human colorectal cancer cells.

Tytuł:
Structure-activity relationship of butyrate analogues on apoptosis, proliferation and histone deacetylase activity in HCT-116 human colorectal cancer cells.
Autorzy:
Ooi CC; CSIRO Preventative Health Flagship, Adelaide, South Australia, Australia.
Good NM
Williams DB
Lewanowitsch T
Cosgrove LJ
Lockett TJ
Head RJ
Źródło:
Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2010 Sep; Vol. 37 (9), pp. 905-11. Date of Electronic Publication: 2010 May 24.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: Oxford, England : Wiley-Blackwell
Original Publication: Oxford, Blackwell Scientific Publications.
MeSH Terms:
Apoptosis/*drug effects
Butyrates/*chemistry
Butyrates/*pharmacology
Cell Proliferation/*drug effects
Colorectal Neoplasms/*physiopathology
Histone Deacetylases/*metabolism
Cyclohexanes ; HCT116 Cells ; HT29 Cells ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; L-Lactate Dehydrogenase/metabolism ; Structure-Activity Relationship
Substance Nomenclature:
0 (Butyrates)
0 (Cyclohexanes)
0 (Histone Deacetylase Inhibitors)
48K5MKG32S (Cyclohexane)
EC 1.1.1.27 (L-Lactate Dehydrogenase)
EC 3.5.1.98 (Histone Deacetylases)
Entry Date(s):
Date Created: 20100526 Date Completed: 20110204 Latest Revision: 20220311
Update Code:
20240104
DOI:
10.1111/j.1440-1681.2010.05403.x
PMID:
20497425
Czasopismo naukowe
1. Butyrate, a bacteria fermentative product in the colonic lumen, has been shown to produce a wide variety of biological effects in human cancer cells in vitro. However, there are pharmacological drawbacks associated with the use of butyrate therapy and there are limited published data on the structure-activity relationship of butyrate analogues in colorectal cancer cells. Previously, we determined structure-activity relationship using HT-29 human colorectal cancer cells. However, it was viewed as important to explore similar relationships in another colorectal cancer cell line. 2. Therefore, in the present study, the in vitro structure-activity relationship of butyrate analogues was examined by investigating their effects on apoptosis, cell proliferation, histone deacetylase (HDAC) activity and lactate dehydrogenase (LDH) leakage as a measure of cell toxicity in HCT-116 human colorectal cancer cells. 3. Of the 32 analogues tested, only 4-benzoylbutyrate, 3-benzo-ylpropionate, 4-(4-nitrophenyl)butyrate and 3-(4-fluorobenzoyl)propionate exhibited comparable biological effects to butyrate. The common structural properties of the compounds of interest were to lack amino or hydroxyl substitutions at the 2-, 3- and/or 4-position of the aliphatic moiety of butyrate. 4. The present study reveals a dissociation between the induction of apoptosis, inhibition of cell proliferation, HDAC activity and LDH leakage. The results indicate differential responses of butyrate analogues in HT-29 and HCT-116 colorectal cancer cells.

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