Zinc Protoporphyrin Suppresses β-Catenin Protein Expression in Human Cancer Cells: The Potential Involvement of Lysosome-Mediated Degradation

Simple item page
dc.contributor.authorShuai Wang
dc.contributor.authorBethany N. Hannafon
dc.contributor.authorStuart E. Lind
dc.contributor.authorWei-Qun Ding
dc.date.accessioned2017-03-05T22:54:58Z
dc.date.available2017-03-05T22:54:58Z
dc.date.issued2015-05-22
dc.descriptionen_US
dc.descriptionen_US
dc.description.abstractZinc protoporphyrin (ZnPP) has been found to have anticancer activity both in vitro and in vivo. We have recently demonstrated that ZnPP diminishes β-catenin protein expression in cancer cells. The present study examined the cellular mechanisms that mediate ZnPP’s suppression of β-catenin expression. We demonstrate that ZnPP induces a rapid degradation of the β-catenin protein in cancer cells, which is accompanied by a significant inhibition of proteasome activity, suggesting that proteasome degradation does not directly account for the suppression. The possibility that ZnPP induces β-catenin exportation was rejected by the observation that there was no detectable β-catenin protein in the conditioned medium after ZnPP treatment of cancer cells. Further experimentation demonstrated that ZnPP induces lysosome membrane permeabilization, which was reversed by pretreatment with a protein transportation inhibitor cocktail containing Brefeldin A (BFA) and Monensin. More significantly, pretreatment of cancer cells with BFA and Monensin attenuated the ZnPP-induced suppression of β-catenin expression in a concentration- and time-dependent manner, indicating that the lysosome protein degradation pathway is likely involved in the ZnPP-induced suppression of β-catenin expression. Whether there is cross-talk between the ubiquitin-proteasome system and the lysosome pathway that may account for ZnPP-induced β-catenin protein degradation is currently unknown. These findings provide a novel mechanism of ZnPP’s anticancer action and reveal a potential new strategy for targeting the β-catenin Wnt signaling pathway for cancer therapy.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationWang S, Hannafon BN, Lind SE, Ding W-Q (2015) Zinc Protoporphyrin Suppresses β-Catenin Protein Expression in Human Cancer Cells: The Potential Involvement of Lysosome-Mediated Degradation. PLoS ONE 10(5): e0127413. doi:10.1371/journal.pone.0127413en_US
dc.identifier.doi10.1371/journal.pone.0127413en_US
dc.identifier.urihttp://hdl.handle.net/11244/49263
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(5): e0127413
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0127413
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectLysosomes,Proteasomes,Zinc,Proteolysis,Protein expression,Permeability,Phosphorylation,Fluorescenceen_US
dc.titleZinc Protoporphyrin Suppresses β-Catenin Protein Expression in Human Cancer Cells: The Potential Involvement of Lysosome-Mediated Degradationen_US
dc.typeResearch Articleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
journal.pone.0127413.pdf
Size:
5.21 MB
Format:
Adobe Portable Document Format
Download

Collections

OU - Faculty and Staff Publications