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A Novel Benzoquinone Compound Isolated from Deep-Sea Hydrothermal Vent Triggers Apoptosis of Tumor Cells.

ABSTRACT: Microorganisms are important sources for screening bioactive natural products. However, natural products from deep-sea microbes have not been extensively explored. In this study, the metabolites of bacteriophage GVE2 -infected (Geobacillus sp. E263 virus) thermophilic bacterium Geobacillus sp. E263, which was isolated from a deep-sea hydrothermal vent, were characterized. A novel quinoid compound, which had anti-tumor activity, was isolated from the phage-challenged thermophile. The chemical structure analysis showed that this novel quinoid compound was 2-amino-6-hydroxy-[1,4]-benzoquinone. The results indicated that 2-amino-6-hydroxy-[1,4]-benzoquinone and its two derivatives could trigger apoptosis of gastric cancer cells and breast cancer cells by inducing the accumulation of intracellular reactive oxygen species. Therefore, our study highlighted that the metabolites from the phage-challenged deep-sea microbes might be a kind of promising sources for anti-tumor drug discovery, because of the similarity of metabolic disorder between bacteriophage-infected microbes and tumor cells.

SUBMITTER: Xu C

PROVIDER: S-EPMC5532642 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:Since deep-sea hydrothermal vent fluids are enriched with toxic metals, it was hypothesized that (i) the biota in the vicinity of a vent is adapted to life in the presence of toxic metals and (ii) metal toxicity is modulated by the steep physical-chemical gradients that occur when anoxic, hot fluids are mixed with cold oxygenated seawater. We collected bacterial biomass at different distances from a diffuse flow vent at 9 degrees N on the East Pacific Rise and tested these hypotheses by examining the effect of mercuric mercury [Hg(II)] on vent bacteria. Four of six moderate thermophiles, most of which were vent isolates belonging to the genus Alcanivorax, and six of eight mesophiles from the vent plume were resistant to >10 microM Hg(II) and reduced it to elemental mercury [Hg(0)]. However, four psychrophiles that were isolated from a nearby inactive sulfide structure were Hg(II) sensitive. A neighbor-joining tree constructed from the deduced amino acids of a PCR-amplified fragment of merA, the gene encoding the mercuric reductase (MR), showed that sequences obtained from the vent moderate thermophiles formed a unique cluster (bootstrap value, 100) in the MR phylogenetic tree, which expanded the known diversity of this locus. The temperature optimum for Hg(II) reduction by resting cells and MR activity in crude cell extracts of a vent moderate thermophile corresponded to its optimal growth temperature, 45 degrees C. However, the optimal temperature for activity of the MR encoded by transposon Tn501 was found to be 55 to 65 degrees C, suggesting that, in spite of its original isolation from a mesophile, this MR is a thermophilic enzyme that may represent a relic of early evolution in high-temperature environments. Results showing that there is enrichment of Hg(II) resistance among vent bacteria suggest that these bacteria have an ecological role in mercury detoxification in the vent environment and, together with the thermophilicity of MR, point to geothermal environments as a likely niche for the evolution of bacterial mercury resistance.

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A Novel Benzoquinone Compound Isolated from Deep-Sea Hydrothermal Vent Triggers Apoptosis of Tumor Cells.

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