NF-κB is the principle
transcription factor and plays the central role in orchestrating chronic
inflammation by regulating levels of
cytokines,
chemokines and
growth factors.
Piperlongumine (PL), a major
alkaloid in the fruit of Piper longum Linn. has gained worldwide attention for its anticancer properties, however, its mechanism of action in the
chemoprevention of
colon cancer has not been investigated yet. Therefore, the present study was designed to elucidate the underlying molecular mechanism of PL in preventing
DMH/DSS induced experimental
colon cancer in mice. In the current study well established
DMH/DSS induced experimental
colon cancer mouse model was used to demonstrate the chemopreventive potential of PL. The expression of NF-κB and its downstream target
proteins was evaluated mainly through western blotting. In addition, CAM assay, immunohistochemical staining and
gelatin zymography was used to show anti-angiogenic and anti-invasive potential of PL. Additionally, important
tumor biomarkers such as
TSA,
LASA, LDH and
IL-6 levels were also estimated. The results of current study showed that PL was capable to inhibit NF-κB activation as well as its nuclear translocation. PL administration to
DMH/DSS treated mice also inhibited the NF-κB downstream signaling cascades such as including COX-2 pathway, JAK/STAT pathway, β-
catenin, Notch signaling pathway, angiogenesis and epithelial to mesenchymal transition pathway. The findings of the present study have claimed PL as promising chemopreventive agent for
colon cancer with pleiotropic action. The current study emphasizes that regular consumption of PL can be an effective approach in the prevention of
colon cancer in humans.