title: 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 E(2) (PGE(2)) 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 PGE(2) 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.
authors.affiliation: Immunology Research Center, Bu-Ali Research Institute .
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Zamani Taghizadeh Rabe
authors.forename: Seyed Hadi
authors.initials: SH
authors.lastname: Mousavi
authors.forename: Nafise
authors.initials: N
authors.lastname: Tabasi
authors.forename: Maryam
authors.initials: M
authors.lastname: Rastin
authors.forename: Shahin
authors.initials: S
authors.lastname: Zamani Taghizadeh Rabe
authors.forename: Zahra
authors.initials: Z
authors.lastname: Siadat
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D041681:NIH 3T3 Cells; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012395:Rose Bengal / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D012395:Rose Bengal; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Apoptosis; Rose Bengal; gastric cancer; macrophage; nitric oxide; prostaglandin E2