Pregled bibliografske jedinice broj: 958331
Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action of a novel hydroxamic acid hybrid molecule
Inhibition of glioblastoma cell proliferation, invasion, and mechanism of action of a novel hydroxamic acid hybrid molecule // Cell death discovery, 4 (2018), 41, 14 doi:10.1038/s41420-018-0103-0 (međunarodna recenzija, članak, znanstveni)
CROSBI ID: 958331 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Inhibition of glioblastoma cell proliferation,
invasion, and mechanism of action of a novel
hydroxamic acid hybrid molecule
Autori
Zhang, Issan ; Beus, Maja ; Stochaj, Ursula ; Le, Phuong, Uyen ; Zorc, Branka ; Rajić, Zrinka ; Petrecca, Kevin ; Maysinger, Dusica
Izvornik
Cell death discovery (2058-7716) 4
(2018);
41, 14
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
glioblastoma ; hybrid molecule ; histone deacetylase inhibitor
Sažetak
Glioblastoma multiforme is one of the most aggressive brain tumors and current therapies with temozolomide or suberoylanilide hydroxamic acid (SAHA, vorinostat) show considerable limitations. SAHA is a histone deacetylase (HDAC) inhibitor that can cause undesirable side effects due to the lack of selectivity. We show here properties of a novel hybrid molecule, sahaquine, which selectively inhibits cytoplasmic HDAC6 at nanomolar concentrations without markedly suppressing class I HDACs. Inhibition of HDAC6 leads to significant α- tubulin acetylation, thereby impairing cytoskeletal organization in glioblastoma cells. The primaquine moiety of sahaquine reduced the activity of Pglycoprotein, which contributes to glioblastoma multiforme drug resistance. We propose the mechanism of action of sahaquine to implicate HDAC6 inhibition together with suppression of epidermal growth factor receptor and downstream kinase activity, which are prominent therapeutic targets in glioblastoma multiforme. Sahaquine significantly reduces the viability and invasiveness of glioblastoma tumoroids, as well as brain tumor stem cells, which are key to tumor survival and recurrence. These effects are augmented with the combination of sahaquine with temozolomide, the natural compound quercetin or buthionine sulfoximine, an inhibitor of glutathione biosynthesis. Thus, a combination of agents disrupting glioblastoma and brain tumor stem cell homeostasis provides an effective anti–cancer intervention
Izvorni jezik
Engleski
Znanstvena područja
Kemija, Temeljne medicinske znanosti, Farmacija
POVEZANOST RADA
Projekti:
MOP-119425
RGPIN 04994-15
IP-09-2014-1501
Ustanove:
Farmaceutsko-biokemijski fakultet, Zagreb
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus