Description
Patulin is a mycotoxin initially produced by species of Penicillum and Aspergillus that is commonly found as a contaminant in apples and apple products. In keratinocytes, patulin increases phosphorylation of EGFR, activates Ras/MAPK/Akt signaling, activates NF-κB, and increases expression of cyclin D1 and COX-2, increasing cell proliferation. Patulin exhibits genotoxic and anticancer activities in a variety of cellular models. Patulin induces DNA damage through the formation of crosslinks. Patulin also activates cleavage of poly(ADP)-ribose polymerase (PARP), increases phosphorylation of EGR-1, and activates caspase 3, resulting in ROS-dependent apoptosis in colorectal cancer cells and leukemia cells. Additionally, patulin decreases transepithelial resistance, altering intestinal epithelial barrier function; this mechanism involves inactivation of protein tyrosine phosphatase.
References
Alam S, Pal A, Kumar R, et al. EGFR-mediated Akt and MAPKs signal pathways play a crucial role in patulin-induced cell proliferation in primary murine keratinocytes via modulation of Cyclin D1 and COX-2 expression. Mol Carcinog. 2013 Jun 29. [Epub ahead of print]. PMID: 23813870.
Glaser N, Stopper H. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796-801. PMID: 22425938.
Kwon O, Soung NK, Thimmegowda NR, et al. Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal. 2012 Apr;24(4):943-50. PMID: 22230687.
Wu TS, Liao YC, Yu FY, et al. Mechanism of patulin-induced apoptosis in human leukemia cells (HL-60). Toxicol Lett. 2008 Dec 15;183(1-3):105-11. PMID: 18992795.
Mahfoud R, Maresca M, Garmy N, et al. The mycotoxin patulin alters the barrier function of the intestinal epithelium: mechanism of action of the toxin and protective effects of glutathione. Toxicol Appl Pharmacol. 2002 Jun 15;181(3):209-18. PMID: 12079430.
