Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: 3/23/2007
Publication Date: 3/23/2007
Citation: Hsiao, S., Wicklow, D.T., Haschek, W. 2007. Cytotoxicity of pyrrocidines in HEPG2 hepatocytes and PK15 renal cells [abstract]. Society of Toxicology. Interpretive Summary:
Technical Abstract: Pyrrocidines are newly reported polyketide-amino acid-derived antibiotics produced by Acremonium zeae, a prevalent seed-borne endophyte of corn. Pyrrocidines exhibited potent activity against Gram-positive bacteria, including drug resistant strains, and displayed significant activity against Candida albicans, as well as fumonisin and alfatoxin producing fungi. In this study, we evaluated the effect of pyrrocidines A and B in two mammalian cell lines, HepG2 cells (a cell line derived from a human hepatocellular carcinoma) and PK15 cells (a cell line derived from a normal pig kidney). The H9C2(2-1) and HepG2 cells were incubated overnight to form monolayers and treated with 0 to 100 µM of pyrrocidine A and B for 24 hours. Cytotoxicity was evaluated by the MTT assay. Pyrrocidine A and B were cytotoxic to both HepG2 and PK15 cells after 24 hours of treatment. ED50 of pyrrocidine A to HepG2 cells was 0.66±0.16 µg/mL and to PK15 cells was 1.03±0.37 µg/mL. Pyrrocidine B was less potent than pyrrocidine A. ED50 of pyrrocidine B to HepG2 was 15.37±4.47 µg/mL and to PK15 was 16.63±5.47 µg/mL. The cytotoxicity of pyrrocidine A to HepG2 cells was more potent than other known mycotoxins, e.g. deoxynivalenol ED50=8.36 µg/mL, fumonisin B1 ED50>100 µg/mL, zearalenone ED50>100 µg/mL, and moniliformin ED50=3.5 µg/mL. A sequential morphological study using time-lapse motion photography suggested that the cell death in PK15 cells induced by pyrrocidine A was consistent with apoptosis. This is the first report of toxicity in a mammalian system. In vivo studies are essential for risk assessment.