Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer

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摘要：

This work reports aLactobacillus rossiaestrain (L. rossiaeD87) isolated from sourdough that synthesizes putrescine - a biogenic amine that raises food safety and spoilage concerns - from arginine via the ornithine decarboxylase (ODC) pathway. TheodcandpotEgenes were identified and sequenced. These genes respectively encode ornithine decarboxylase (Odc), which participates in the decarboxylation of ornithine to putrescine, and the ornithine/putrescine exchanger (PotE), which exchanges ornithine for putrescine. Transcriptional analysis showed thatodcandpotEform an operon that is regulated transcriptionally by ornithine in a dose-dependent manner. To explore the possible role of the ODC pathway as an acid stress resistance mechanism for this bacterium, the effect of acidic pHs on its transcriptional regulation and on putrescine biosynthesis was analysed. Acidic pHs induced the transcription of theodc-potEgenes and the production of putrescine over that seen at neutral pH. Further, putrescine production via the ODC system improved the survival ofL. rossiaeD87 by counteracting the acidification of the cytoplasm when the cells were subjected to acidic conditions. These results suggest the ODC pathway ofL. rossiaeD87 provides a biochemical defence mechanism against acidic environments.

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关键词：

polyamines, ornithine decarboxylase, polyamine analogs, spermidine/spermine N<sup>1</sup>-acetyl transferase, spermine oxidase, bis(ethyl)polyamine analogs, breast cancer, MCF-7 cells, transgenic mice

DOI：

10.3390/medsci6010024

年份：

2018