Biosafety and Selective Cytotoxicity of Kojic and Ellagic Acids in Salivary Gland Carcinoma: A Preclinical Perspective

Salivary gland carcinomas (SGCs) are rare, aggressive tumors with high histopathological diversity and resistance to conventional therapies. The need for novel therapeutic approaches has drawn attention to natural compounds with antitumor potential.

Objective: This study aims to investigate the in vitro and in ovo cytotoxic and safety profiles of two natural agents, kojic acid (KA) and ellagic acid (EA), on human submandibular salivary gland carcinoma (A253) cells and human immortalized keratinocytes (HaCaT), as well as to assess their irritant potential via the HET-CAM assay. The cytotoxicity and morphological changes of A253 and HaCaT cells were evaluated using the MTT assay and brightfield microscopy. The HET-CAM assay was applied to evaluate the irritant effects of the compounds in ovo. Both KA and EA reduced A253 cell viability in a dose-dependent manner, with the highest cytotoxicity observed at 100 µM. In contrast, HaCaT cells maintained high viability and exhibited no notable morphological alterations post-treatment, supporting the selectivity of the compounds. HET-CAM scores for both KA and EA fell within the non-irritant range (IS=0.07), further confirming their biosafety. KA and EA exhibit promising antitumor activity against A253 salivary gland carcinoma cells, with minimal toxicity toward normal epithelial cells and no significant irritation potential. These findings justify further investigation of these compounds for their potential use as adjuvant agents in the treatment of salivary gland carcinoma (SGC).