Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.13.3 (
histidine kinase
)
2,405
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hydroxyketone chelators, deferiprone (
HK1
), maltol (HK3) and their related compounds (HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. Most hydroxyketones except HK6 showed relatively higher tumor-specific cytotoxicity. Deferiprone (
HK1
), which showed the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3) in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma HSC-2 cell lines. The cytotoxic activity of
HK1
against HL-60 and HSC-2 cells was reduced in the presence of
FeCl3
, while that of HK3 was significantly increased by
FeCl3
. Agarose gel electrophoresis showed that
HK1
induced internucleosomal DNA fragmentation in HL-60 cells, but the addition of
FeCl3
inhibited the DNA fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of
FeCl3
. In HSC-2 cells,
HK1
and 3 did not induce DNA fragmentation in the presence or absence of
FeCl3
. Colorimetric protease assay showed that
HK1
activated the caspase 3, 8 and 9 in HL-60 cells. On the other hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of
FeCl3
.
HK1
and 3 also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.
...
PMID:Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines. 1516 Oct 23
