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: UMLS:C0684249 (
lung carcinoma
)
23,830
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It has recently been reported that radiation enhances mitochondrial energy metabolism in various tumor cell lines. To examine how this radiation-induced alteration in mitochondrial function influences tumor cell viability, various lipophilic triphenylphosphonium (
TPP
+
) cation derivatives and related compounds such as 4-hydroxy-2,2,6,6-tetramethyl-1-oxy-piperidin (Tempol) with
TPP
+
(named "Mito-") were designed to inhibit the mitochondrial electron transport chain. Mito-(CH
2
)
10
-Tempol (M10T) and its derivatives, Mito-(CH
2
)
5
-Tempol (M5T), Mito-(CH
2
)
10
-Tempol-Methyl (M10T-Me), Mito-C
10
H
21
(M10), and C
10
H
21
-Tempol (10T), were prepared. In HeLa human cervical adenocarcinoma cells and A549 human
lung carcinoma
cells, the fractional uptake of the compound into mitochondria was highest among the TTP
+
analogs conjugated with Tempol (M10T, M5T, and 10T). M10T, M10T-Me, and M10 exhibited strong cytotoxicity and enhanced X-irradiation-induced reproductive cell death, while 10T and M5T did not. Furthermore, M10T, M10T-Me, and M10 decreased basal mitochondrial membrane potential and intracellular ATP. M10T treatment inhibited X-ray-induced increases in ATP production. These results indicate that the
TPP
cation and a long hydrocarbon linker are essential for radiosensitization of tumor cells. The reduction in intracellular ATP by lipophilic
TPP
+
is partly responsible for the observed radiosensitization.
...
PMID:Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells. 2809 83
