Title

Extremophilic microbes from acidic mine waste lake produce novel anticancer compounds

Presentation Type

Poster

Abstract

Berkeley Pit Lake in Butte, Montana is part of the largest superfund site in the United States. This abandoned open pit copper mine is filled with acidic water (pH 2.5) and high levels of heavy metals. In 1995, the Stierle Lab discovered life in the form of fungi and bacteria in the Pit and has since found over sixty other extremophiles in the lake water and basal sediment. My project in the Stierle Lab focuses on the isolation, structural characterization, and bioactivity assessment of metabolites produced by the actinomycete PS-45A-4, a branching bacterium found in the sediment of the Pit. Metabolites from the broth culture of this microbe are isolated by size exclusion and silica gel column chromatography guided by specific signal transduction enzyme inhibition assays. Up-regulation of the signal transduction enzymes matrix metalloproteinase-3 (MMP-3) and caspase-1 has been associated with inflammation as well as the onset and metastasis of cancer cells; therefore, inhibition of these enzymes could have therapeutic value. Metabolites isolated from broth cultures of PS-45A-4 that demonstrate significant inhibition of MMP-3 or caspase-1 will be evaluated in the National Cancer Institute human cancer cell line screen and in the intact inflammasome assay. Research has shown strong correlations between MMP-3 inhibition and reduced cancer cell activities including tumor initiation and metastasis. Caspase-1 inhibition has been shown to mitigate production of pro-inflammatory cytokines in the inflammasome and to target inflammation-associated cancers. Once anti-cancer activity of a compound is confirmed, the structure of the novel, bioactive metabolites will be determined. 1D and 2D proton NMR and mass spectrometry are used to determine the exact structure of the compound. Discovering novel anti-cancer compounds from biological sources is important to the continuing search for safe and effective cancer treatments.

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Apr 13th, 11:00 AM Apr 13th, 12:00 PM

Extremophilic microbes from acidic mine waste lake produce novel anticancer compounds

UC Ballroom

Berkeley Pit Lake in Butte, Montana is part of the largest superfund site in the United States. This abandoned open pit copper mine is filled with acidic water (pH 2.5) and high levels of heavy metals. In 1995, the Stierle Lab discovered life in the form of fungi and bacteria in the Pit and has since found over sixty other extremophiles in the lake water and basal sediment. My project in the Stierle Lab focuses on the isolation, structural characterization, and bioactivity assessment of metabolites produced by the actinomycete PS-45A-4, a branching bacterium found in the sediment of the Pit. Metabolites from the broth culture of this microbe are isolated by size exclusion and silica gel column chromatography guided by specific signal transduction enzyme inhibition assays. Up-regulation of the signal transduction enzymes matrix metalloproteinase-3 (MMP-3) and caspase-1 has been associated with inflammation as well as the onset and metastasis of cancer cells; therefore, inhibition of these enzymes could have therapeutic value. Metabolites isolated from broth cultures of PS-45A-4 that demonstrate significant inhibition of MMP-3 or caspase-1 will be evaluated in the National Cancer Institute human cancer cell line screen and in the intact inflammasome assay. Research has shown strong correlations between MMP-3 inhibition and reduced cancer cell activities including tumor initiation and metastasis. Caspase-1 inhibition has been shown to mitigate production of pro-inflammatory cytokines in the inflammasome and to target inflammation-associated cancers. Once anti-cancer activity of a compound is confirmed, the structure of the novel, bioactive metabolites will be determined. 1D and 2D proton NMR and mass spectrometry are used to determine the exact structure of the compound. Discovering novel anti-cancer compounds from biological sources is important to the continuing search for safe and effective cancer treatments.