Inhibition of 12-LOX and COX-2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K-Akt signalling pathways

dc.contributor.author Agarwal, Smita
dc.contributor.author Achari, Chandrani
dc.contributor.author Praveen, D.
dc.contributor.author Roy, Karnati R.
dc.contributor.author Reddy, Gorla Venkateswara
dc.contributor.author Reddanna, Pallu
dc.date.accessioned 2022-03-27T01:04:16Z
dc.date.available 2022-03-27T01:04:16Z
dc.date.issued 2009-11-01
dc.description.abstract Eicosanoids, the oxygenated metabolites of arachidonic acid (AA), mediate a variety of human diseases, such as cancer, inflammation and arthritis. To evaluate the role of eicosanoids in epidermoid carcinoma, the expression of AA metabolizing enzymes, such as lipoxygenases (LOXs) and cyclooxygenases (COXs), was analysed in a human epidermoid carcinoma cell line (A431). These studies revealed overexpression of 12-R-LOX and COX-2 in A431 cells. Baicalein (a 12-LOX inhibitor) and celecoxib (a COX-2 inhibitor) significantly reduced thymidine incorporation, whereas 12-(R)-HETE and 12-(S)-HETE (12-LOX metabolites) and PGE2 (COX-2 metabolite) significantly enhanced thymidine incorporation, suggesting a role for these enzymes in the regulation of A431 cell proliferation. Further studies on the mechanism of cell death by baicalein and celecoxib revealed that the induction of apoptosis in A431 cells was associated with reduction in the Bcl-2/Bax ratio, release of cytochrome c, activation of caspase-3 and PARP cleavage. The apoptosis induced by baicalein and celecoxib was mediated by down regulation of ERK and PI3K-Akt pathways. Further, 12-(R)-HETE, 12-(S)-HETE and PGE2 upregulated the p-ERK and p-Akt levels, suggesting the involvement of ERK and Akt pathways in the 12-LOX- and COX-2-mediated regulation of growth in A431 cells. Our findings suggest that 12-R-LOX and COX-2 play a critical role in the regulation of growth in epidermoid carcinoma and that their inhibitors may be of potential therapeutic importance. © 2009 John Wiley & Sons A/S.
dc.identifier.citation Experimental Dermatology. v.18(11)
dc.identifier.issn 09066705
dc.identifier.uri 10.1111/j.1600-0625.2009.00874.x
dc.identifier.uri https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2009.00874.x
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/4067
dc.subject 12-R-LOX
dc.subject Akt
dc.subject Apoptosis
dc.subject COX-2
dc.subject ERK
dc.title Inhibition of 12-LOX and COX-2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K-Akt signalling pathways
dc.type Journal. Article
dspace.entity.type
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