Phytic acid regulates proliferation of colorectal cancer cells by downregulating NF-kB and β-catenin signalling

Abstract

Objectives: Phytic acid (PYT) also known as inositol hexakisphosphate or inositol polyphosphate has shown a broad range of biological effects including anti-inflammatory, antioxidant, and anticancer effects in several preclinical studies. This study aimed to investigate the effects of PYT in vitro on HCT116 and HT-29 cell lines and to analyse the intricate mechanism of NF-κB-β-catenin signalling pathways. Material and methods: Both cell lines were treated with PYT, and analysed for cell viability, apoptosis, progression of cell cycle, and DNA fragmentation. Gene and protein expression analysis was performed to assess the molecular mechanism. Results: PYT suppressed the proliferation of colorectal cancer cell lines in a dose- and time-dependent manner with an estimated IC50 value of 2.96 and 3.35 mm, respectively. PYT caused cell cycle arrest at the G2/M phase in both CRC cell lines and induced mitochondrial intrinsic apoptosis via activation of caspase-9 and caspase-3 cascade. PYT suppressed the expression of pro-inflammatory markers especially COX-2 and iNOS, and IL-lβ, IL-6, and IL-10. Analysing the mechanism behind the effects of PYT showed that it suppressed the levels of NF-κB and β-catenin and inhibited the levels of cyclin Dl and c-Myc (its downstream targets) and COX-2. Conclusion: The results collectively indicate the potent anti-inflammatory and anti-proliferative effects of PYT in CRC cell lines that were mediated by downregulating the β-catenin and NF-κB signalling pathways. Results advocate that natural supplementation of PYT can be an effective preventive approach in controlling cancer of colorectal region.