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Histone deacetylase inhibitor OBP‑801 and amrubicin synergistically inhibit the growth of squamous cell lung carcinoma by inducing mitochondrial ASK1‑dependent apoptosis.
- Source :
-
International journal of oncology [Int J Oncol] 2020 Mar; Vol. 56 (3), pp. 848-856. Date of Electronic Publication: 2020 Jan 24. - Publication Year :
- 2020
-
Abstract
- Squamous cell lung carcinoma (SQCLC) is an aggressive type of lung cancer. In contrast with the marked advances that have been achieved in the treatment of lung adenocarcinoma, there are currently no effective targeted therapies for SQCLC, for with cytotoxic drugs are still the main treatment strategy. Therefore, the present study aimed to develop novel combination therapies for SQCLC. The results demonstrated that a combined treatment with the potent histone deacetylase (HDAC) inhibitor OBP‑801 and the third‑generation anthracycline amrubicin synergistically inhibited the viability of SQCLC cell lines by inducing apoptosis signal‑regulating kinase 1 (ASK1)‑dependent, as well as JNK‑ and p38 mitogen‑activated protein kinase (MAPK)‑independent apoptosis. OBP‑801 treatment strongly induced the protein expression levels of thioredoxin‑interacting protein (TXNIP), and amrubicin treatment increased the levels of intracellular reactive oxygen species (ROS), which suggested that this combination oxidized and dissociated thioredoxin 2 (Trx2) from mitochondrial ASK1 and activated ASK1. Moreover, mouse xenograft experiments using human H520 SQCLC cells revealed that the co‑treatment potently suppressed tumor growth in vivo. These results suggested that a combined treatment with OBP‑801 and amrubicin may have potential as a therapeutic strategy for SQCLC.
- Subjects :
- Animals
Anthracyclines pharmacology
Carcinoma, Non-Small-Cell Lung metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Drug Synergism
Female
Gene Expression Regulation, Neoplastic drug effects
Histone Deacetylase Inhibitors pharmacology
Humans
Lung Neoplasms metabolism
Mice
Peptides, Cyclic pharmacology
Xenograft Model Antitumor Assays
Anthracyclines administration & dosage
Carcinoma, Non-Small-Cell Lung drug therapy
Histone Deacetylase Inhibitors administration & dosage
Lung Neoplasms drug therapy
MAP Kinase Kinase Kinase 5 metabolism
Peptides, Cyclic administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 56
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 32124968
- Full Text :
- https://doi.org/10.3892/ijo.2020.4969