Deciphering the cancer chemopreventive potential of phytochemicals: an integrative perspective on molecular targets and signaling networks.

Cell death, cell proliferation, cell differentiation, cell invasion and cell migration are the fundamental cellular processes which are dysregulated due to the perturbed cell signaling pathways leading to cancer. These biological pathways leading to cancer are intertwined. Genes controlling these pathways are mutated due to the various cellular insults and hence result in cancer stem cells that proliferate without the normal regulatory molecular switches seen in noncancerous cells. The important cellular signaling pathways which are known to malfunction in cancer cells include NF–κB, Akt, MAPK, Wnt, Notch, p53, EGFR, etc. among many others. Bio-active molecules that can regulate signal transduction pathways in cancerous cells have recently emerged as a popular research area in biomedicine. Bio-molecules or phytochemicals modulate the signaling pathways and are widely appreciated as anti-cancer agents synergizing with the chemotherapy. Wnt signaling has been implicated in the tumorigenesis and is an attractive therapeutic target. Similarly, polyphenols are known to have an effect on the caspase cascade and are known to play a modulatory role in the process of apoptosis by interfering with the PI3K/Akt cell signaling pathway. EGFR is elevated in tumorigenesis, and phytochemicals are known to have downregulating effects by inhibiting the protein tyrosine activities of PTK of EGFR. Nuclear factor- kB has been well documented to be aberrant in the cell signaling pathway and is looked at as an important therapeutic target. Therefore, many investigators have focused on finding the molecular targets of these natural phyto-compounds. Since aberrant cell signaling plays a central role in cancer progression, the subject of the review is the activity of phytochemicals as bioactive regulators of the pathways, i.e., Wnt, NF-kB, and PI3K/Akt, with insights provided into the mechanism by which they can be used as complementary anti-cancer agents.