Development of NOSH-NSAIDs: A new class of anti-inflammatory pharmaceuticals for the treatment of cancer

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have anti-cancer (chemopreventive) properties; however, side effects preclude their long-term use. NOSH-NSAIDs, designed as safer alternatives, are novel hybrid chimaeras that release nitric oxide (NO) and hydrogen sulfide (H2S). NOSH-NSAIDs are gastrointestinally safe yet retain all the pharmacological properties of their native NSAID. NOSHNSAIDs are orders of magnitude more potent than their conventional counterparts in inhibiting the growth of various human cancer cell lines of different tissue origins, adenomatous, epithelial and lymphocytic. This growth inhibition is a result of a reduction in cell proliferation and cell cycle arrest, leading to increased apoptosis. In xenograft mouse models of cancer, NOSH-aspirin was better than normal aspirin as a chemopreventive agent; it dose-dependently inhibited tumour growth and tumour mass. NOSH-naproxen was significantly more efficacious than normal naproxen in reducing the growth of established tumours.