Abstract 2186: The novel nitric oxide and hydrogen sulfide releasing anti-cancer agent, NBS-1120, protects the GI tract from the ulcerogenic activity of aspirin and naproxen

Abstract

Abstract NBS-1120 is a member of the novel ‘enhanced NSAID’ class of anti-cancer agents that release nitric oxide and hydrogen sulfide targeting tumor inflammatory pathways while inducing ROS, caspases and apoptosis and inhibiting proliferation, beta catenin and FOXM1, ultimately impacting the regulation of NF-kB. NBS-1120, a derivative of aspirin that is devoid of GI side effects, demonstrated potent anti-cancer activity in vitro and in vivo while maintaining all the classical pharmacological/therapeutic activities of aspirin. Cancer pain takes many forms and is managed by a variety of pain medications that include NSAIDs. Because of their anti-inflammatory activity, NSAIDs may be particularly helpful in moderate and severe pain arising from bone cancer or metastatic lesions. A patient may be on a low-dose aspirin regimen as an antithrombotic but may need an NSAID such as naproxen for moderate to severe cancer pain. In these situations, GI side effects are a major concern. Commonly, a proton pump inhibitor (PPI) is co-administered to minimize GI injury. While significantly reducing upper GI side effects, recent animal studies suggest that suppression of acid secretion leads to exacerbation of NSAID-induced small intestinal injury and bleeding. Here, we investigated whether NBS-1120, itself protective against GI injury, could also protect the GI tract from the ulcerogenic activity of aspirin and naproxen. In an acute study, male rats (n=4/gp), were treated with naproxen; aspirin then naproxen; or NBS-1120 then naproxen. 6 h post naproxen, rats were euthanized, stomachs removed, cut along the greater curvature and the number and length (mm) of all hemorrhagic lesions (ulcer index, UI) recorded. In a chronic study, animals were pretreated with Lansoprazole then with aspirin and naproxen or NBS-1120 and naproxen. UI was determined for stomach and jejunum as above. Results: Acute studies UI: naproxen = 35.5±7.2 mm; aspirin + naproxen = 47.8±8.8 mm; NBS-1120 + naproxen = 4.5±10 mm. Chronic studies: PPI alone = 0 mm; PPI + aspirin + naproxen = 10±5 mm; PPI + NBS-1120 + naproxen = 0 mm. Jejunum ulceration: PPI alone = 0 mm; PPI + aspirin + naproxen = 15.8±6.8 mm; PPI + NBS-1120 + naproxen = 2±3 mm. Aspirin + naproxen result in significant upper GI damage; this was mitigated to a considerable degree by pretreatment with Lansoprazole. However, this regimen moved the problem to the jejunum, causing bleeding. In both acute and chronic studies NBS-1120 protected the GI tract against naproxen and/or aspirin injury. Significantly, in a chronic study with Lansoprazole, NBS-1120 reduced naproxen and aspirin induced jejunum ulceration. Molecular targets affected by these treatment regiments are currently under investigation. These data suggest that the anti-cancer agent, NBS-1120, can be combined safely with other NSAIDs and protects against GI injury. Citation Format: Jan J. Scicinski, Mark El-Miniawi, Tasneem Zahran, Khosrow Kashfi. The novel nitric oxide and hydrogen sulfide releasing anti-cancer agent, NBS-1120, protects the GI tract from the ulcerogenic activity of aspirin and naproxen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2186.