The p53 inhibitor, pifithrin-α, disrupts microtubule organization, arrests growth, and induces polyploidy in the rainbow trout gill cell line, RTgill-W1.
Pifithrin-α (PFT-α) blocks p53-dependent transcription and is an example of the many drugs being developed to target the p53 pathway in humans that could be released into the environment with potential impacts on aquatic animals if they were to become successful pharmaceuticals. In order to understand how p53 drugs might act on fish, the effects of PFT-α on rainbow trout gill epithelial cell line, RTgill-W1, were studied. PFT-α was not cytotoxic to RTgill-W1 in cultures with or without fetal bovine serum (FBS), but at 5.25μg/ml, PFT-α completely arrested proliferation. When FBS was present, PFT-α increased the number of polyploid cells over 12days. Those results suggest that like in mammals, p53 appears to regulate ploidy in fish. However, several effects were seen that have not been observed with mammalian cells. PFT-α caused a transient rise in the mitotic index and a disruption in cytoskeletal microtubules. These results suggest that in fish cells PFT-α affects microtubules either directly through an off-target action on tubulin or indirectly through an on-target action on p53-regulated transcription.
Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Fanxing
F
Zeng
Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Xiang
X
Yu
Aquatic Contaminants Research Division, Environment Canada, Burlington, ON, Canada L7R 4A6.
James P
JP
Sherry
Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Brian
B
Dixon
Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
Bernard P
BP
Duncker
Department of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1. Electronic address: ncbols@uwaterloo.ca.
Niels C
NC
Bols
D000818:Animals; D052160:Benzothiazoles / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D016158:Genes, p53 / Q000187:drug effects* / Q000502:physiology; D005880:Gills / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000633:toxicity*; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology; D017686:Oncorhynchus mykiss; D011123:Polyploidy; D014050:Toluene / Q000031:analogs & derivatives* / Q000633:toxicity
D052160:Benzothiazoles; D006131:Growth Inhibitors; D014050:Toluene; C121565:pifithrin
Cell cycle arrest; Microtubules; Pifithrin-α; Polyploidy; RTgill-W1; p53