Hyperbaric oxygen increases glioma cell sensitivity to antitumor treatment with a novel isothiourea derivative in vitro
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Oncology Reports
ISSN
1021-335X
EISSN
1791-2431
Wydawca
SPANDIDOS PUBL LTD
DOI
URL
Rok publikacji
2019
Numer zeszytu
5
Strony od-do
2703-2716
Numer tomu
41
Identyfikator DOI
Liczba arkuszy
1.58
Słowa kluczowe
en
cancer
glioblastoma
hyperbaric oxygen therapy
hypoxia
isothiourea derivatives
Open access
Tryb otwartego dostępu
Inne
Wersja tekstu w otwartym dostępie
Wersja opublikowana
Licencja otwartego dostępu
Creative Commons — Uznanie autorstwa
Czas opublikowania w otwartym dostępie
Razem z publikacją
Data udostępnienia w sposób otwarty
Streszczenia
Język
en
Treść
Glioblastoma (GBM) is the most common primary brain tumor. Tumor hypoxia is a pivotal factor responsible for the progression of this malignant glioma, and its resistance to radiation and chemotherapy. Thus, improved tumor tissue oxygenation may promote greater sensitivity to anticancer treatment. Protein kinase D1 (PKD1) protects cells from oxidative stress, and its abnormal activity serves an important role in multiple malignancies. The present study examined the effects of various oxygen conditions on the cytotoxic potential of the novel isothiourea derivate N,N `-dimethyl-S-(2,3,4,5,6-pentabromobenzyl)- isothiouronium bromide (ZKK-3) against the T98G GBM cell line. ZKK-3 was applied at concentrations of 10, 25 and 50 mu M, and cells were maintained under conditions of normoxia, anoxia, hypoxia, hyperbaric oxygen (HBO), hypoxia/hypoxia and hypoxia/HBO. The proliferation and viability of neoplastic cells, and protein expression levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha), PKD1, phosphorylated (p)PKD1 (Ser 916) and pPKD1 (Ser 744/748) kinases were evaluated. Oxygen deficiency, particularly regarding hypoxia, could diminish the cytotoxic effect of ZKK-3 at 25 and 50 mu M and improve T98G cell survival compared with normoxia. HBO significantly reduced cell proliferation and increased T98G cell sensitivity to ZKK-3 when compared with normoxia. HIF-1 alpha expression levels were increased under hypoxia compared with normoxia and decreased under HBO compared with hypoxia/hypoxia at 0, 10 and 50 mu M ZKK-3, suggesting that HBO improved oxygenation of the cells. ZKK-3 exhibited inhibitory activity against pPKD1 (Ser 916) kinase; however, the examined oxygen conditions did not appear to significantly influence the expression of this phosphorylated form in cells treated with the tested compound. Regarding pPKD1 (Ser 744/748), a significant difference in expression was observed only for cells treated with 10 mu M ZKK-3 and hypoxia/hypoxia compared with normoxia. However, there were significant differences in the expression levels of both phosphorylated forms of PKD1 under different oxygen conditions in the controls. In conclusion, the combination of isothiourea derivatives and hyperbaric oxygenation appears to be a promising therapeutic approach for malignant glioma treatment.
Cechy publikacji
discipline:Biologia medyczna
discipline:Medycyna
discipline:Medical biology
discipline:Medicine
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:912115
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