NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model
Abstract
Highlights: Black-Right-Pointing-Pointer NOSH-aspirin is the first dual acting NO and H{sub 2}S releasing hybrid. Black-Right-Pointing-Pointer Its IC{sub 50} for cell growth inhibition is in the low nano-molar range. Black-Right-Pointing-Pointer Structure-activity studies show that the sum of the parts does not equal the whole. Black-Right-Pointing-Pointer NOSH-aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H{sub 2}S) can increase mucosal defense mechanisms has led to the development of NO- and H{sub 2}S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H{sub 2}S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC{sub 50}s of 45.5 {+-} 2.5, 19.7 {+-} 3.3, and 7.7 {+-} 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G{sub 0}/G{sub 1} cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold moremore »
- Authors:
-
- Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031 (United States)
- Department of Physiology, Indiana University School of Medicine, South Bend, IN 46617 (United States)
- Publication Date:
- OSTI Identifier:
- 22207754
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 419; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ACETYLSALICYLIC ACID; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; HYBRIDIZATION; HYDROGEN SULFIDES; IN VITRO; INFLAMMATION; INHIBITION; LARGE INTESTINE; MICE; NEOPLASMS; NITRIC OXIDE
Citation Formats
Chattopadhyay, Mitali, Kodela, Ravinder, Olson, Kenneth R., and Kashfi, Khosrow. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model. United States: N. p., 2012.
Web. doi:10.1016/J.BBRC.2012.02.051.
Chattopadhyay, Mitali, Kodela, Ravinder, Olson, Kenneth R., & Kashfi, Khosrow. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model. United States. https://doi.org/10.1016/J.BBRC.2012.02.051
Chattopadhyay, Mitali, Kodela, Ravinder, Olson, Kenneth R., and Kashfi, Khosrow. 2012.
"NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model". United States. https://doi.org/10.1016/J.BBRC.2012.02.051.
@article{osti_22207754,
title = {NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model},
author = {Chattopadhyay, Mitali and Kodela, Ravinder and Olson, Kenneth R. and Kashfi, Khosrow},
abstractNote = {Highlights: Black-Right-Pointing-Pointer NOSH-aspirin is the first dual acting NO and H{sub 2}S releasing hybrid. Black-Right-Pointing-Pointer Its IC{sub 50} for cell growth inhibition is in the low nano-molar range. Black-Right-Pointing-Pointer Structure-activity studies show that the sum of the parts does not equal the whole. Black-Right-Pointing-Pointer NOSH-aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H{sub 2}S) can increase mucosal defense mechanisms has led to the development of NO- and H{sub 2}S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H{sub 2}S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC{sub 50}s of 45.5 {+-} 2.5, 19.7 {+-} 3.3, and 7.7 {+-} 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G{sub 0}/G{sub 1} cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation.},
doi = {10.1016/J.BBRC.2012.02.051},
url = {https://www.osti.gov/biblio/22207754},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 419,
place = {United States},
year = {Fri Mar 16 00:00:00 EDT 2012},
month = {Fri Mar 16 00:00:00 EDT 2012}
}