Therapeutic investigation of Jania rubens polysaccharides: antimicrobial activity and potentiation of chemotherapy in colorectal cancer cells

BACKGROUND: Sulfated polysaccharides (SPs) isolated from the marine red macroalga Jania rubens exhibit diverse biological activities. Streptococcus agalactiae (S. agalactiae) poses a particular risk to immunocompromised individuals, including cancer patients. Colorectal cancer (CRC) remains a major cause of cancer-related mortality, and resistance to chemotherapeutics such as doxorubicin (DOX) continues to limit treatment outcomes. This study investigated the antibacterial activity of Lebanese J. rubens SPs against S. agalactiae and evaluated their potential to enhance the efficacy of vancomycin and doxorubicin in human colorectal cancer cell lines (HCT-116, HT-29, Caco-2). METHODS: Antibacterial activity was assessed using the agar well diffusion method, across extracts, tested at 50–4000 µg/mL. The Minimum Inhibitory Concentration (MIC) was determined and synergistic interactions of SPs and vancomycin were evaluated using the fractional inhibitory concentration index (FICI). Biofilm inhibition assays were conducted, and RT-PCR quantified the expression of genes involved in adhesion and immune evasion. Carbohydrate content was measured using the phenol–sulfuric acid method. Synergistic cytotoxic effects with DOX were evaluated in colorectal cancer cell lines (HCT-116, HT-29, Caco-2) using viability assays, and cytotoxicity was examined in the normal-like colon epithelial cell line NCM460D. RESULTS: SP extracts demonstrated strong antibacterial activity against S. agalactiae, even at lowest concentration tested, with an MIC of 0.39 µg/mL. Synergy with vancomycin was confirmed by FICI values and accompanied by significant inhibition of biofilm formation. The SP–vancomycin combination downregulated key virulence-associated genes, reducing cylE, fbsB2 and CpsG by 74.6%, 21.5%, 15.3%, respectively. Carbohydrate analysis indicated a glucose-rich composition (1.84 mg/mL). In cancer models, SPs markedly enhanced DOX cytotoxicity, lowering cell viability to 11% in HCT-116, 38% in HT-29, and 15% in Caco-2, compared with 58%, 87%, and 68% with DOX alone. Minimal cytotoxicity was observed in NCM460D cells, 96% at 50 µg/mL and 86% at 100 µg/mL. CONCLUSION: These findings indicate that the Lebanese Jania rubens sulfated polysaccharide extract exhibits dual in-vitro activities, demonstrating antibacterial effects against S. agalactiae and enhancing the in-vitro cytotoxic effect of doxorubicin in colorectal cancer cell lines. Further mechanistic and in-vivo studies are required to clarify these activities and better understand their underlying basis.