Marine microbial arginase: a metabolic therapeutic strategy for oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) represents a significant clinical burden, with limited advancements in metabolic-targeted therapies. Arginase is a metalloenzyme that plays an essential role in the hydrolysis of L-arginine into urea and L-ornithine. In recent years, arginase enzyme also shows promising role in therapeutic especially in anti-cancer therapy through arginine deprivation therapy (ADT). Among many tumors that are arginine-auxotrophic due to downregulation of ASS1 are hepatocellular carcinoma, melanoma, and subsets of oral cancers, and are therefore susceptible to depletion of extracellular arginine. Although recombinant human arginase has advanced to preclinical and clinical trials, issues such as immunological reactions and limited stability have sparked interest in alternative sources. Marine microorganisms, especially from deep-sea environments, are known to produce unique and stable enzymes with high catalytic efficiency and are less prone to protein denaturation. As a result of their remarkable stability in harsh conditions and variety of structures, marine microbial arginases have emerged as the top candidates for investigation. In addition to remaining active at varying pH, salinity, and temperatures, these enzymes offer a versatile platform for protein engineering and therapeutic optimisation. This review focuses on the biochemical and structural properties of arginase, compares microbial and human forms, and explores the mechanisms of its antitumor action, including tumor cell growth inhibition, angiogenesis modulation, and immune suppression within the tumor microenvironment. Additionally, it identifies developments in marine bioprospecting, combination strategies with immunotherapy, and nanoparticle-based delivery as major trends influencing future research.