Ruthenium-Enhanced Curcumin Derivatives Targets Tumor Growth and Cancer-Related Inflammation in Head and Neck Cancer Models

Kateřina Veselá¹Ameneh Tatar¹Zdeněk Kejík¹Nikita Abramenko¹Robert Kaplanek¹Petr Babula²Kateřina Kučnirová¹Jan Hajduch¹Pavel Martásek¹Milan Jakubek^1*

• ¹First Faculty of Medicine, Charles University, Prague, Czechia
• ²Masarykova univerzita, Brno, Czechia

Head and neck cancers (HNC) remain a significant clinical challenge, particularly due to their association with chronic inflammation triggered by tobacco carcinogens and human papillomavirus (HPV) infection. Persistent activation of pro-inflammatory and pro-angiogenic pathways, including NF-κB, IL-6, and IL-8, plays a crucial role in tumor progression. In this study, we present novel ruthenium-enhanced curcumin derivatives (complexes 3 and 4) as promising agents with both anti-inflammatory and anticancer properties. Complex 3 demonstrated potent cytotoxic and antiproliferative effects across both HPV-negative and HPV-positive HNC cell lines, while complex 4 showed selectivity toward oral squamous cell carcinoma (OSCC). Both complexes exhibited cytostatic and migrastatic activities. Importantly, treatment with these complexes significantly suppressed NF-κB activity and reduced IL-6 and IL-8 levels more effectively than native curcumin. These findings highlight their potential not only as stand-alone therapeutic agents but also as adjuvants in combination therapies for HNC.