Mo1164 The Duel Nitric Oxide and Hydrogen Sulfide-Releasing Nonsteroidal Anti-Inflammatory Drugs NOSH-Aspirin, NOSH-Naproxen, and NOSH-Sulindac Are Safe to the Stomach and Have Strong Anti-Inflammatory, Analgesic, Antipyretic, Anti-Platelet, and Anti-Cancer Properties

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used to treat pain, fever, and inflammation. However, mounting evidence shows that NSAIDs, such as aspirin, have very promising antineoplastic properties. The chemopreventive, antiproliferative behaviour of NSAIDs has been associated with both their inactivation of cyclooxygenases (COX) and their ability to induce apoptosisviapathways that are largely COX-independent. In this review, the various proapoptotic pathways induced by traditional and novel NSAIDs such as phospho-NSAIDs, hydrogen sulfide-releasing NSAIDs and nitric oxide-releasing NSAIDs in mammalian cell lines are discussed, as well as the proapoptotic effects of NSAIDs on budding yeast which retains the hallmarks of mammalian apoptosis. The significance of these mechanisms in terms of the role of NSAIDs in effective cancer prevention is considered.

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NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

Redox Biology ◽

10.1016/j.redox.2015.08.012 ◽

2015 ◽

Vol 6 ◽

pp. 287-296 ◽

Cited By ~ 32

Author(s):

Khosrow Kashfi ◽

Mitali Chattopadhyay ◽

Ravinder Kodela

Keyword(s):

Nitric Oxide ◽

Hydrogen Sulfide ◽

Anti Cancer ◽

Anti Inflammatory

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Ethanesulfohydroxamic Acid Ester Prodrugs of Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Synthesis, Nitric oxide and Nitroxyl Release, Cyclooxygenase Inhibition, Anti-inflammatory, and Ulcerogenicity Index Studies

Journal of Medicinal Chemistry ◽

10.1021/jm101403g ◽

2011 ◽

Vol 54 (5) ◽

pp. 1356-1364 ◽

Cited By ~ 49

Author(s):

Zhangjian Huang ◽

Carlos A. Velázquez ◽

Khaled R. A. Abdellatif ◽

Morshed A. Chowdhury ◽

Julie A. Reisz ◽

...

Keyword(s):

Nitric Oxide ◽

Acid Ester ◽

Cyclooxygenase Inhibition ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Ester Prodrugs

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Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals

Journal of Neurochemistry ◽

10.1046/j.1471-4159.2001.00205.x ◽

2001 ◽

Vol 76 (6) ◽

pp. 1895-1904 ◽

Cited By ~ 122

Author(s):

Masato Asanuma ◽

Sakiko Nishibayashi-Asanuma ◽

Ikuko Miyazaki ◽

Masahiro Kohno ◽

Norio Ogawa

Keyword(s):

Nitric Oxide ◽

Neuroprotective Effects ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Potential role of acetylsalicilic acid and other non-steroidal anti-inflammatory drugs in cancer risk reduction (literature review)

Zaporozhye Medical Journal ◽

10.14739/2310-1210.2021.3.209851 ◽

2021 ◽

Vol 23 (3) ◽

Author(s):

V. V. Buheruk ◽

O. B. Voloshyna ◽

L. I. Kovalchuk ◽

I. V. Balashova ◽

O. V. Naidionova

Keyword(s):

Cancer Risk ◽

Acetylsalicylic Acid ◽

Potential Role ◽

Task Force ◽

Current Systematic Review ◽

Anti Cancer ◽

Cancer Types ◽

Inflammatory Drugs ◽

Anti Inflammatory

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.

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Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

Molecules ◽

10.3390/molecules26164957 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4957

Author(s):

Wanda Baer-Dubowska ◽

Maria Narożna ◽

Violetta Krajka-Kuźniak

Keyword(s):

Signaling Pathways ◽

Oleanolic Acid ◽

Short Review ◽

Therapeutic Effects ◽

Pentacyclic Triterpenoid ◽

Anti Cancer ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Synthetic Derivatives ◽

Cancer Activity

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.

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The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032006000300015 ◽

2006 ◽

Vol 43 (3) ◽

pp. 233-237 ◽

Cited By ~ 3

Author(s):

Afonso Luiz Villa ◽

Ceneviva Reginaldo ◽

Fernanda Viaro ◽

Fernando Ramalho ◽

Antonio Dorival Campos ◽

...

Keyword(s):

Nitric Oxide ◽

Isosorbide Dinitrate ◽

Saline Solution ◽

Isotonic Saline ◽

Nitric Oxide Donor ◽

Group Iii ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Gastric Mucous ◽

Lesion Index

BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared to each other. CONCLUSION: Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.

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