Background: Colorectal cancer (CRC) ranks third among all cancer-related deaths around the globe. Chemotherapy may
prolong the survival of CRC patients to some extent, but its clinical use is associated with grave side effects on overall health. Contrary to
chemotherapy, the use of plant-derived therapeutic molecules offered advantages because of their reduced toxicity. Polyphenol is group
of phytochemicals that impart many therapeutic benefits in the treatment of diabetes, cardiovascular disease and cancer. Various
signaling pathways, including Wnt/β-catenin, MAPK/PI3K and TGF-β/Smad play very important roles in the development and
progression of CRC. Polyphenols inhibit CRC progressions by modulating these signaling pathways e. g. curcumin and resveratrol
impede cancer cell proliferation by inhibiting Wnt signaling. Because of their lower aqueous solubility, the therapeutic efficacy of
polyphenols is not fully exploited. In order to increase their bioavailability and efficacy, the nanoformulations of polyphenols have been
formulated and investigated against various CRC test models. The main objective of this review is to explore the potential roles of
polyphenols and their nanoformulations in the treatment of colorectal cancer.
Methods: We used PubMed, Web of Science, ScienceDirect, Google scholar and Scopus electronic databases by searching the keywords:
Nanoparticles, Polyphenols, Colorectal cancer, Cell signaling pathways. Mostly, the articles were retrieved directly from the journals
licensed to the library of Qassim University, Saudi Arabia.
Results: Literature analysis has shown that the polyphenols contains several important bioactive compounds, which showed potential
effectiveness against CRC. Incorporating polyphenols into nanoparticles further enhanced their bioavailability and efficacy. The findings
from various studies demonstrated that polyphenol-nanoformulations accelerated the apoptosis in CRC cells by upregulating the levels of
caspases and Bax, whereas inhibiting the CRC cell proliferation by dowregulating the expression of Bcl-2 and ERK1/2.
Conclusions: This review provides a valuable resource on the important anti-CRC role of polyphenols and their nanoformulations. This
review will expand our knowledge about the anti-CRC roles of polyphenols and their mechanisms of action through the multiple cell