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ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo.
- Source :
-
Pharmacological research [Pharmacol Res] 2016 Dec; Vol. 114, pp. 67-73. Date of Electronic Publication: 2016 Oct 21. - Publication Year :
- 2016
-
Abstract
- Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H <subscript>2</subscript> S-NSAIDs). They consist of a traditional NSAID to which an H <subscript>2</subscript> S-releasing moiety is covalently attached. We have recently demonstrated that H <subscript>2</subscript> S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H <subscript>2</subscript> S-releasing derivative of naproxen, ATB-346 [2-(6-methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H <subscript>2</subscript> S. We used cell culture and a mouse melanoma model to evaluate the effect of ATB-346 on: i) in vitro growth of human melanoma cells; ii) in vivo melanoma development in mice. Cell culture studies demonstrated that ATB-346 reduced the in vitro proliferation of human melanoma cells and this effect was associated to induction of apoptosis and inhibition of NF-κB activation. Moreover, ATB-346 had novel Akt signaling inhibitory properties. Daily oral dosing of ATB-346 (43μmol/kg) significantly reduced melanoma development in vivo. This study shows that ATB-346, a novel H <subscript>2</subscript> S-NSAID, inhibits human melanoma cell proliferation by inhibiting pro-survival pathways associated with NF-κB and Akt activation. Furthermore, oral treatment with ATB-346 inhibits melanoma growth in mice. In conclusion, the combination of inhibition of cyclooxygenase and delivery of H <subscript>2</subscript> S by ATB-346 may offer a promising alternative to existing therapies for melanoma.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Chemokines immunology
Female
Humans
Hydrogen Sulfide immunology
Melanoma immunology
Melanoma pathology
Mice, Inbred C57BL
NF-kappa B immunology
Naproxen pharmacology
Naproxen therapeutic use
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Antineoplastic Agents therapeutic use
Melanoma drug therapy
Naproxen analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 114
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 27777130
- Full Text :
- https://doi.org/10.1016/j.phrs.2016.10.019