Efficacy of natural antiinflammatories in primary rat tracheal epithelial cell transformation. Free

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We have developed and used a primary rat tracheal epithelial (RTE) cell transformation model for identifying potential chemopreventive agents belonging to different chemical classes/biological activity. The current study examined whether natural products with significant anti-inflammatory characteristics have chemopreventive activity in the same model system. RTE cells were treated with B[a]P alone or with five nontoxic concentrations of a natural anti-inflammatory product and the resulting foci at the end of 30 days were scored for inhibition of transformation. EP-1A, a sea cucumber fraction containing saponins, was tested at 0.01-1.0 µg/mL and it inhibited transformation in a dose-dependent manner with an IC₅₀ of 0.1µg/ml. Similarly, CbrA5, a lipid fraction from sea cucumber, inhibited transformation at all concentrations (0.3-10µg/mL) with 100% inhibition at the highest dose and an IC₅₀ of 0.3µg/mL. Green oil, another lipid compound from sea cucumber significantly inhibited B[a]P-induced transformation (0.1-10µg/mL) in a reverse dose-dependent manner with an IC₅₀ of 0.1µg/mL. Frondanol, an oil extract from sea cucumber, was the only fraction that was not effective in this model. Iloprost, a stable prostacyclin analogue was highly effective (44-100 %) at higher concentrations (30-100 µM). Turmerin, a water soluble small peptide from turmeric, exhibited dose-dependent response with maximum inhibition (37%) at 10 µg/mL. In addition, turmerin showed excellent correlation between inhibition of transformation and effect on CK-14, survivin and apoptosis, biomarkers that appear at different stages of RTE transformation. The agents were rated based on the IC₅₀ concentration from low high as follows: EP-1A ≤ Green oil< CBr5 <Turmerin<Iloprost. It appears that the RTE model system can be successfully employed to identify natural antiinflammotories, another class of cancer preventive agents. It is highly likely that these agents being natural products, have multiple biological activities which has contributed to their effectiveness in this primary cell respiratory model of transformation (Supported by NCI #N01-CN-43301).