Antitumour activity of 3-nitropropionic acid from Phomopsis sp and optimization of fermentation conditions

作者：Lu F T; Ma D C; Yan W; Guo J; Bai L H^*

来源：Letters in Applied Microbiology, 2015, 61(2): 165-170.

DOI：10.1111/lam.12437

• 3-nitropropionic acid
• antitumour activity
• apoptosis
• Bcl-2 signalling pathway
• caspase-3-independent
• fermentation condition optimization

In this study, 3-nitropropionic acid (3-NPA) was separated and purified from endophytic fungi belonging to Phomopsis sp. and its cytotoxicity was determined by MTT assay. Treatment with 3-NPA for 24h resulted in a dose-dependent apoptosis in MCF-7 cells. Through quantitative detection of the genes that are closely related to the Bcl-2 signalling pathway, there was an increased expression of p53 and Bax and a decreased expression of Bcl-2, which indicated apoptosis in these cells. Meanwhile, the overexpression of PARA (poly ADP-ribose polymerase) and apoptosis inducing factor (AIF) also suggested that 3-NPA induced cellular apoptosis through a caspase-3-independent pathway in caspase-3-deficient MCF-7 cells. The fermentation condition was also improved to produce more 3-NPA: glucose as a carbon source and yeast extract as a nitrogen source, fermentation for 8days at 32 degrees C and a solution environment of pH 50. Under these conditions, the yield of 3-NPA was increased to 529mgl(-1) compared with 410mgl(-1) under traditional fermentation conditions.
Significance and Impact of the Study3-Nitropropionic acid is a mitochondrial inhibitor and has some useful bioactivities such as antibacterial activity. In this paper we found that 3-NPA also has obvious cytotoxicity, so we studied its antitumour activity and tried to determine the antitumour molecular mechanism, opening a new perspective for potential antitumour prodrug development. As 3-NPA is often obtained from natural products with a low yield, in order to overcome thedisadvantage of an endophytic fungi source of 3-NPA, we optimized the fermentation conditions for 3-NPA in Phomopsis sp. to obtain the maximum production of 3-NPA.

• 出版日期2015-8
• 单位四川大学