eNSAIDs and Cancer

NOSH Platform and enhanced NSAIDs

NOSH Platform and Cancer

eNSAIDs are designed from existing NSAID scaffolds and release key signaling gases, nitric oxide and hydrogen sulfide on dosing. NSAIDs that release nitric oxide or hydrogen sulfide have been shown to reduce the occurrence of cancer, however they do not possess sufficient activity to treat cancer.

In contrast, eNSAIDs have been shown to be effective anti-cancer agents in animal tumor models. Although the combination of these two gases and the released NSAID contribute to the anti-cancer activity of eNSAIDs, importantly, eNSAID activity is greater than the sum of their constituent parts.

NSAIDs and Cancer

NSAIDs are protective against cancer

A key link between cancer and inflammation is that the use of NSAIDs, such as aspirin, reduces risk and mortality. Over 30 epidemiological studies, collectively describing results on more than 1 million individuals, have established NSAIDs as the prototypical chemopreventive agents against many forms of cancer. In particular, three well-designed randomized, double-blind trials of aspirin as a chemopreventive agent against colorectal adenomas established its chemopreventive effect. These studies have expanded to underscore the chemopreventive effects of NSAIDs in general against colon, breast, pancreas, bladder, head and neck, oesophageal, ovarian, prostate, hepatocellular and skin cancers. In particular two recent reports indicated that daily aspirin use resulted in reductions in cancer incidence and mortality, and also prevented distant metastasis.

Pharmacological effects of NBS-1120. NBS-1120 does not cause gastric damage, it is a potent anti-inflammatory, and has anti-platelet, analgesic and anti-pyretic activity. In vitro, NBS-1120 reduces cell proliferation, causes G0/G1 cell cycle arrest, leading to increased apoptosis; and in vivo it reduces tumor growth and tumor mass in mice. (Kodela et al., 2015)

A comparison of the in vitro activity of NBS-1120 vs. compounds representing its consituent parts. SNAP is was used to deliver nitric oxide, while ADT-OH was used to deliver hydrogen sulfide. Note that NBS-1120 is very significantly more active compared to dosing Aspirin, ADT-OH and SNAP, the constituent parts of NBS-1120.

Effect of eNSAIDs on

Cancer

NBS-1120 (NOSH-ASA) in a mouse breast cancer model

This video shows details from an experiment to compare the effect of dosing NBS-1120 (NOSH-Aspirin) against control in a model of human breast cancer in immunocompromised mice. As described in the video, the mice were inncolulated with ER -ve breast cancer cells and the tumors allowed to grow to approx. 50 mm³. The mice were then separated into two groups of five. One group was treated daily with NBS-1120, the other group did not receive any treatment. After approximately one month, both groups of mice had the same weight and identical movement and behaviour suggesting no drug-related toxicity. In the control group, tumors had grown to 1000-1200 mm³ while the tumors in the treated animals were significantly smaller with at least one mouse being completely tumor free. Similar experiments have been carried out in mice bearing ER+ve breast, SW480 colon cancer and pancreatic cancer tumors. All eNSAID compounds have similar effects in treated animals.

NBS-1120 Prevents Growth of HT-29 Human Colon Cancer Cells in Mouse Model

This figure compares the activity of NBS-1120 against the injection solution alone as a control.

Athymic nude mice that were inoculated subcutaneously were treated with NBS-1120 (100 mg/kg) or the vehicle control after the tumors had reached an average size of 80 mm3. Treatment with NBS-1120 or control was continued for 18 days and tumor sizes were measured every 3 days.

The upper panel shows representative photographs of the mice from each group: Vehicle on the left and NBS-1120 (NOSH-ASA) on the right.

The lower panel shows the mean change in tumor volume over time (each group has four animals) together with the standard deviation at each time point.