Combination of 5-aminosalicylic acid and hyperthermia synergistically enhances apoptotic cell death in HSC-3â¯cells due to intracellular nitric oxide/peroxynitrite generation.
Cancer Lett
; 451: 58-67, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30867139
ABSTRACT
The repurposing of existing FDA-approved non-cancer drugs is a potential source of new treatment options for cancer patients. An anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), has been clinically used to treat inflammatory bowel disease. Hyperthermia (HT) is widely applicable addendum therapy with the existing cancer treatment modalities. Here, we addressed how 5-ASA combined with HT induces lethal effects in human oral squamous cell carcinoma (OSCC) HSC-3â¯cells. We found that 5-ASA/HT combination significantly inhibited the viability of HSC-3â¯cells, while cytotoxic effects in primary human dermal fibroblast cells were minor. Apoptotic endpoints were significantly increased by the 5-ASA/HT combined treatment, as evidenced by presence of Annexin V-FITC/PI positive cells, loss of MMP, Bcl-2/Bax ratio alteration, and increased Fas, cleaved Bid, and caspase expression. Interestingly, the enhancement of apoptosis was reversed in the presence of ON/ONOO- scavengers. These findings indicate that the combination treatment enhances apoptosis via ON/ONOO- mediated ER stress-Ca2+-mitochondria signaling and caspase-dependent apoptotic pathways. Our findings provide novel evidence that the combination of 5-ASA and HT is a promising approach for the enhancement of apoptosis; it may serve as an effective strategy for treating human OSCC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Mesalamina
/
Ácido Peroxinitroso
/
Febre
/
Óxido Nítrico
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article