Prodigiosin is a biologically active secondary metabolite produced by various microorganisms and is a natural red pigment [1]. Prodigiosin is an effective inhibitor of the Wnt/β-catenin pathway and regulates cancer metabolism by inhibiting the rate and level of intracellular ATP production [2,3]. Prodigiosin has antibacterial, anti-cancer, antiviral and immunosuppressive properties [1,4].
In vitro, after treating HEK293T cells expressing Wnt1 with Prodigiosin(50, 100, 250, 500nM) for 24 hours, the Wnt/β-catenin signaling cascade reaction was significantly inhibited. The concentration of Prodigiosin at 25-500nM in MDA-MB-231 and MDA-MB-468 breast cancer cell lines significantly inhibited Wnt/β-catenin signaling and cyclin D1 levels in breast cancer cells, suppressed cell proliferation and induced cell apoptosis [3]. Treatment of HCT116 cells with Prodigiosin(0.25, 0.5, 1, 2μM) for 2 hours significantly inhibited the intracellular ATP generation rate and level, thereby suppressing the growth of cancer cells [4].
In vivo, Prodigiosin (1, 3, 5μg/ml) was intraperitoneally infused and administered to rat lung injury models established by cecal ligation and perforation (CLP). Seven days later, Prodigiosin exerted anti-inflammatory and antioxidant effects by down-regulating the NF-κB/NLRP3 signaling axis. Thereby alleviating acute lung injury in rat models of rheumatoid arthritis [5].
References:
[1]Islan GA, Rodenak-Kladniew B, Noacco N, Duran N, Castro GR. Prodigiosin: a promising biomolecule with many potential biomedical applications. Bioengineered. 2022 Jun;13(6):14227-14258.
[2] Yang HA, Han TH, Haam K, Lee KS, Kim J, Han TS, Lee MS, Ban HS. Prodigiosin regulates cancer metabolism through interaction with GLUT1. Nat Prod Res. 2024 Jun 24:1-8.
[3]Wang Z, Li B, Zhou L, Yu S, Su Z, Song J, Sun Q, Sha O, Wang X, Jiang W, Willert K, Wei L, Carson DA, Lu D. Prodigiosin inhibits Wnt/β-catenin signaling and exerts anticancer activity in breast cancer cells. Proc Natl Acad Sci U S A. 2016 Nov15;113(46):13150-13155.
[4]Han R, Xiang R, Li J, Wang F, Wang C. High-level production of microbial Prodigiosin: A review. J Basic Microbiol. 2021 Jun;61(6):506-523.
[5]Chen P, Wu H, Bian T, Yang L, Jiang H. Prodigiosin improves acute lung injury in a rat model of rheumatoid arthritis via down-regulating the nuclear factor kappaB/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 signaling pathway. J Physiol Pharmacol. 2023 Feb;74(1).
Prodigiosin是由多种微生物产生的具有生物活性的次生代谢产物，是一种天然的红色素[1]。Prodigiosin是Wnt/β-连环蛋白（Wnt/β-catenin）途径的有效抑制剂，并且通过抑制细胞内ATP的产生速率和水平来调节癌症代谢[2,3]。Prodigiosin具有抗菌、抗癌、抗病毒以及免疫抑制特性[1,4]。
在体外，Prodigiosin(50、100、250、500nM)处理表达Wnt1的HEK293T细胞24小时后显著抑制Wnt/β-catenin信号级联反应。Prodigiosin在MDA-MB-231和MDA-MB-468乳腺癌细胞系中以25~500nM的浓度显著抑制乳腺癌细胞中Wnt/β-catenin信号传导和细胞周期蛋白D1水平，进一步抑制细胞增值并诱导细胞凋亡[3]。Prodigiosin(0.25、0.5、1、2μM)处理HCT116细胞2小时显著抑制细胞内ATP生成速率和水平，从而抑制癌细胞生长[2]。
在体内，Prodigiosin（1、3、5μg/ml）对通过盲肠结扎穿孔（CLP）建立的大鼠肺损伤模型腹腔输注给药，7天后，Prodigiosin通过下调NF-κB/NLRP3信号轴发挥抗炎和抗氧化作用，从而减轻类风湿性关节炎大鼠模型的急性肺损伤[5]。