Flavonoids and Wnt/β-catenin signaling: potential role in colorectal cancer therapies

Abstract

It is now well documented that natural products have played an important role in anticancer therapy. Many studies focus on the ability of these natural compounds to modulate tumor-related signaling pathways and the relationship of these properties to an anticancer effect. According to the World Health Organization (WHO), colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death among men and women. Therefore, finding strategies to fight against CRC is an emergent health problem. CRC has a strong association with deregulation of Wnt/β-catenin signaling pathway. As some types of natural compounds are capable of modulating the Wnt/β-catenin signaling, one important question is whether they could counteract CRC. In this review, we discuss the role of flavonoids, a class of natural compounds, on Wnt/β-catenin regulation and its possible potential for therapeutic usage on colorectal cancer.

Figure 1

Wnt/β-catenin signaling pathway. (A) In absense of Wnt; (B) after binding of Wnt-ligand. APC, adenomatous poyposis coli; CK1, casein kinase1; Dkk, dickkopf; Dvl, disheveled; β-Trcp, beta-transducin repeat containing; GSK3, glycogen synthase kinase 3; LRP 5/6, LDL receptor-related protein 5/6; TCF, T cell factor. From APC: FRP, frizzled related protein; WIF, Wnt inhibitor factor; HDAC, histone deacetylase; Tnks, tankyrases; LEF, lymphoid enhancer-binding fator; PAR, poly (ADP-ribose); TLE, transducin-like enhancer proteins.

Figure 2

Scheme of colon cancer cells progression. (A) The progression of mutations that commonly lead to colorectal cancer; (B) Scheme that represent the four stage of colorectal cancer (CRC): Stage I–IV: Note that CRC in Stage IV is in lymph node and has spread to at least one distant organ.