ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy.
Aged
AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase
/ antagonists & inhibitors
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
/ genetics
Anthraquinones
/ pharmacology
Biomarkers, Tumor
/ genetics
Female
Follow-Up Studies
Head and Neck Neoplasms
/ drug therapy
Humans
Ketoglutaric Acids
/ metabolism
Male
Middle Aged
Prognosis
Squamous Cell Carcinoma of Head and Neck
/ drug therapy
Substrate Specificity
Tumor Cells, Cultured
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 09 2019
13 09 2019
Historique:
received:
14
04
2019
accepted:
27
08
2019
entrez:
15
9
2019
pubmed:
15
9
2019
medline:
31
10
2020
Statut:
epublish
Résumé
The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. Considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.
Identifiants
pubmed: 31519943
doi: 10.1038/s41598-019-49550-x
pii: 10.1038/s41598-019-49550-x
pmc: PMC6744417
doi:
Substances chimiques
Anthraquinones
0
Biomarkers, Tumor
0
Ketoglutaric Acids
0
ALKBH3 protein, human
EC 1.14.11.-
AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase
EC 1.14.11.-
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
EC 1.14.11.33
FTO protein, human
EC 1.14.11.33
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13249Références
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