# Ruthenium-enhanced curcumin derivatives target tumor growth and cancer-related inflammation in head and neck cancer models

## TL;DR

This study develops new curcumin derivatives with ruthenium that inhibit cancer growth and inflammation in head and neck cancer models more effectively than curcumin alone.

## Contribution

The novel ruthenium-enhanced curcumin derivatives show improved anti-inflammatory and anticancer effects in HNC models.

## Key findings

- Complex 3 showed potent cytotoxicity in both HPV-negative and HPV-positive HNC cell lines.
- Both complexes suppressed NF-kB activity and reduced IL-6 and IL-8 levels more effectively than native curcumin.
- Complex 4 demonstrated selectivity toward oral squamous cell carcinoma.

## Abstract

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 proinflammatory and proangiogenic pathways, including nuclear factor kappa B (NF-kB), interleukin 6 (IL-6), and interleukin 8 (IL-8), plays a crucial role in tumor progression.

In this study, we synthetized ruthenium-enhanced curcumin derivatives (complexes 3 and 4) and study their anti-inflammatory and anticancer properties by using HNC cell lines.

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-kB 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.

Chemical structures of ruthenium complexes are shown with their associated cytotoxicity values (IC₅₀/SCC-9): Compound 3 exhibits higher cytotoxicity at 4.7 micromolar, while compound 4 shows lower cytotoxicity at 14.3 micromolar. Illustrated pathway depicts that increased NF-kB activity in cells lead to IL-6 and IL-8 secretion and thereby cancer dissemination. But, Compound 3 and 4 are direct inhibitor of NF-kB signalling and they direct target IL-6 and IL-8.