A review. Preface.Nitric Oxide (NO) is an odorless, colorless gas first identified by Joseph Priestley in 1774, which was described to be toxic and highly reactive. It is now widely acknowledged that they are produced endogenously and have important biol. roles in most mammalian tissues.The important role of NO in human biol. was recognized in 1992, when the journal Science introduced NO as the "Mol. of the Year" and in 1998, Robert Furchgott, Louis Ignarro and Ferid Murad were awarded the Nobel Prize in Physiol. or Medicine 'for their discoveries concerning nitric oxide as a signaling mol. in the cardiovascular system'. What led to this recognition were three principal discoveries: (i) Ferid Murad discovered that NO could activate the cytosolic isoform of guanylyl cyclase (sGC), thereby catalyzing the conversion of GTP to cyclic GMP, which established the NO-cyclic GMPpathway; (ii) Robert Furchgott demonstrated that relaxation of isolated preparations of blood vessels by acetylcholine (Ach) requires the presence of endothelial cells and that ACh, acting on muscarinic receptors of these cells, stimulates release of one or more substances that cause relaxation of the vascular smooth muscle, thus discovering the endothelium-derived relaxing factor or EDRF; and(iii) Louis Ignarro identi¹ed that EDRF is NO, thereby establishing that mammalian cells produce NO.The goal of this meeting series is to promote the exchange of ideas between diverse scientists from around the world who do not usually attend the same conferences but have a common interest in nitric oxide and cancers.The organizers of the New York meeting decided to expand the theme of the work shop to go "beyond" cancer and also to include some presentations on the role of hydrogen sulfide. The underlying thought being to bring about discussions on the many similarities on the roles and potential interactions of these two gas o-transmitters.

2020-06-01·Biochemical pharmacology

NOSH-aspirin (NBS-1120) inhibits pancreatic cancer cell growth in a xenograft mouse model: Modulation of FoxM1, p53, NF-κB, iNOS, caspase-3 and ROS

Article

作者: Khosrow Kashfi ; Niharika Nath ; Mitali Chattopadhyay ; Ravinder Kodela ; Gabriela Santiago ; Thuy Tien C. Le

Pancreatic cancer has poor survival rates and largely ineffective therapies. Aspirin is the prototypical anti-cancer agent but its long-term use is associated with significant side effects. NOSH-aspirin belongs to a new class of anti-inflammatory agents that were designed to be safer alternatives by releasing nitric oxide and hydrogen sulfide. In this study we evaluated the effects of NOSH-aspirin against pancreatic cancer using cell lines and a xenograft mouse model. NOSH-aspirin inhibited growth of MIA PaCa-2 and BxPC-3 pancreatic cancer cells with IC₅₀s of 47 ± 5, and 57 ± 4 nM, respectively, while it did not inhibit growth of a normal pancreatic epithelial cell line at these concentrations. NOSH-aspirin inhibited cell proliferation, caused G₀/G₁ phase cycle arrest, leading to increased apoptosis. Treated cells displayed increases in reactive oxygen species (ROS) and caspase-3 activity. In MIA PaCa-2 cell xenografts, NOSH-aspirin significantly reduced tumor growth and tumor mass. Growth inhibition was due to reduced proliferation (decreased PCNA expression) and induction of apoptosis (increased TUNEL positive cells). Expressions of ROS, iNOS, and mutated p53 were increased; while that of NF-κB and FoxM1 that were high in vehicle-treated xenografts were significantly inhibited by NOSH-aspirin. Taken together, these molecular events and signaling pathways contribute to NOSH-aspirin mediated growth inhibition and apoptotic death of pancreatic cancer cells in vitro and in vivo.

2015-12-01·Biochemical pharmacology2区 · 医学

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

2区 · 医学

Article

作者: Chattopadhyay, Mitali ; Velázquez-Martínez, Carlos A ; Kodela, Ravinder ; Kashfi, Khosrow

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass.

100 项与 NBS-1120 相关的药物交易

登录后查看更多信息