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:C0017638 (
glioma
)
30,880
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Radiation is a current standard treatment of
glioma
. The fractionated radiotherapy with low dose of radiation over weeks has been employed in
glioma
patients, while radiotherapy can only offer palliation due to the radioresistance. We cumulatively radiated a glioblastoma cell line, U87MG, and screened radioresistant
glioma
cells. A transcriptome sequencing was performed to analyze the transcription differences between the raidoresistant and control cells, which showed the mitochondria
NADH-ubiquinone oxidoreductase
(Complex I) subunits were up-regulated in the radioresistant cells. The copy numbers of mitochondria were increased in the radioresistant
glioma
cells. After using mitochondria Complex I inhibitors, rotenone and metformin, to treat
glioma
cells, we found the resistant
glioma
cells re-sensitized to radiation. These results demonstrate that Complex I is associated with the fractioned radiation-induced radioresistance of
glioma
and would be a potent target for clinical radiotherapy of
glioma
.
...
PMID:Inhibition of mitochondria NADH-Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation. 3276 50
The FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and
glioma
. Analogous to the mechanism of action proposed in parasites, ATO inhibits mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, we developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains (Mito
4
-ATO, Mito
10
-ATO, Mito
12
-ATO, and Mito
16
-ATO). Results show, for the first time, that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depending upon the alkyl chain length, the molecular target of inhibition changes from mitochondrial complex III to
complex I
. Mito
4
-ATO and Mito
10
-ATO inhibit both pyruvate/malate-dependent
complex I
and duroquinol-dependent complex III-induced oxygen consumption whereas Mito
12
-ATO and Mito
16
-ATO inhibit only
complex I
-induced oxygen consumption. Mitochondrial target shifting may have immunoregulatory implications.
...
PMID:Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone. 3308 70
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