Piroxicam and c-phycocyanin prevent colon carcinogenesis by inhibition of membrane fluidity and canonical Wnt/β-catenin signaling while up-regulating ligand dependent transcription factor PPARγ

The colon cancer tissues from DMH treated rats exhibited higher membrane potential, fluidity and changed lipid order as examined by Merocyanine 540 and 1,6-diphenyl-1,3,5-hexatriene, respectively. A transition from gel to liquid crystalline state was observed by Laurdan fluorescence and also reduced fluorescence quenching of NBD-PE as contributed in the decreased membrane lipid phase separation. With piroxicam, a traditional NSAID and c-phycocyanin, a biliprotein from Spirulina platensis, these effects were normalized. An augmented intracellular Ca+2 had contributed to the drug mediated apoptosis which is supported by an elevated calpain-9 expression. Histopathologically, a large pool of secreted acid/neutral mucopolysaccrides as well as the presence of blood vessels and dysplastic crypts signifies invasive mucinous adenocarcinoma while both the drugs reduced these neoplastic alterations. Wnt/β-catenin pathway was also found to be up-regulated which served as a crucial indicator for cancer cell growth. A concomitant down regulation of PPARγ was noted in DMH treatment which is associated with tumor progression. The expression of PPARα and δ, the other two isoforms of PPAR family was also modulated. We conclude that piroxicam and c-phycocyanin exert their anti-neoplastic effects via regulating membrane properties, raising calpain-9 and PPARγ expression while suppressing Wnt/β-catenin signaling in experimental colon carcinogenesis.