Rose Bengal suppresses gastric cancer cell proliferation via apoptosis and inhibits nitric oxide formation in macrophages

Abstract

Rose Bengal (RB) has been used as a safe agent in clinical diagnosis. In addition, it is used as a photodynamic sensitizer for removing microorganisms and cancer cells. Recently, its preferential toxicity after direct exposure to cancer cells was proven. The present study focuses on anti-cancer and anti-inflammatory activities of RB. The toxicity of RB against AGS gastric cancer and NIH 3T3 fibroblast cell lines was studied using an MTT assay. Patterns of any cell death among the AGS cells were defined using Annexin-V and PI staining. In addition, the effect of RB on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production induced by lipopolysaccha-ride in J774A.1 macrophages was determined. Modulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions in the macrophages was also evaluated by Western blots. The results showed that AGS cells exhibited significant concentration-dependent decreases in growth in response to RB; these cells showed a greater growth inhibition than did non-malignant 3T3 cells, suggesting that anti-growth activity of RB could be cell-specific. Moreover, AGS cells exposed to RB exhibited a significant increase in apoptosis; only at high RB doses did the cells display significant levels of necrosis. While RB also caused a modest decrease in the growth of J774A.1 macrophages, the cells displayed remarkable decreases in NO production and iNOS expression without significant concurrent modulation in PGE₂ production or COX-2 expression. The data from this study appears to suggest that RB differentially impacts on transformed cell lines, preferentially suppresses growth of a gastric cancer cell line through induction of apoptosis, and induces changes in cells that could reflect potential anti-inflammatory effects that might be induced in situ.

• Apoptosis
• gastric cancer
• macrophage
• nitric oxide
• prostaglandin E₂
• Rose Bengal

Acknowledgements

The authors would like to thank the authorities in the research council of Mashhad University of Medical Sciences (MUMS) for their financial support (Grant #85497).