On the other hand, the dysregulation of the Wnt/β-catenin pathway is often associated with a variety of diseases, including cancer. The Wnt/β-catenin signaling pathway, also known as the canonical Wnt signaling pathway, plays a crucial role in numerous biological processes, such as embryonic development, the regulation of the cell cycle, apoptosis and many others. The antiproliferative effect of licochalcone A (LiA a natural chalcone isolated from the root of Chines licorice, Glycyrrhiza inflata) in different gastric cancer cell lines has also been associated with the inhibition of the cell cycle at the G2/M phase with the simultaneous down-regulation of cyclin A and cyclin B expression. This effect has been associated with the down-regulation of survivin and the activation of caspase-3. The cumulation of cells in the G2/M phase of the cell cycle has also been observed in 2′,4′-dihydroxychalcone-treated MGC-803 cells. Among other effects, this chalcone-induced G2/M arrest was followed by the activation of caspases-3 and -9, indicating the mitochondrial pathway of apoptosis. documented a strong antiproliferative effect of the newly synthesized quinoline chalcone derivative 12e against the MGC-803 gastric cancer cell line. Similar to their activity in colon cancer cells, chalcones also mostly stop cell cycle progression at the G2/M phase in gastric cancer cells. Furthermore, both natural and synthetic chalcones have been studied as potential anticancer agents in gastric carcinogenesis models. In addition, several other publications have revealed an association between p53 activation and apoptosis induction in chalcone-treated colon cancer cells. Interestingly, they also found apoptosis induction in p53-null HCT116 cells, suggesting that both p53-dependent and p53-independent mechanisms can play roles in apoptosis that is induced by this chalcone. showed a high level of p53 and apoptosis induction in chalcone-treated HCT116 cells. On the other hand, colon cancer cells with mutated p53 have been found to be insensitive to sappanchalcone treatment. Its phosphorylation (i.e., activation) and subsequent caspase activation have been observed in sappanchalcone-treated HCT116 cells. Īnother important player in apoptosis regulation is the protein p53, which is a tumor suppressor activated by DNA damage. Moreover, a decrease in MMP has also often been detected. In various colon cancer cells, chalcone treatment leads to either the activation of the proapoptotic members of the Bcl-2 protein family (e.g., Bax and Bad) or the suppression of antiapoptotic proteins (e.g., Bcl-xL and Bcl-2), resulting in the release of several proapoptotic proteins (e.g., cytochrome and Smac/DIABLO) and the activation of initiator caspase 9 or execution caspases 3/7. The modulation of Bcl-2 protein family activity leads to the permeabilization of mitochondrial outer membrane, the loss of mitochondrial membrane potential (MMP) and the subsequent release of proapoptotic factors, followed by caspase activation and cell death. The structure and function of mitochondria are significantly changed in cells that have been exposed to apoptotic stimuli. Several studies have demonstrated the ability of chalcones to induce the intrinsic apoptosis (mitochondrial) pathway. Ĭhalcones play important role in the induction of both intrinsic and extrinsic apoptosis pathways. A detailed review of chalcones as tubulin polymerization inhibitors has also been released recently. documented the sulfonamide chalcone-induced G2/M arrest of colorectal adenocarcinoma metastatic cells with subsequent cell death. The G2/M arrest associated with the dysregulation of cyclin A and B1 expression has also been observed in xanthohumol (Xn)-treated HT-29 cells. These chalcones also modulated the levels of cell cycle regulatory proteins, as evidenced by the downregulation of cyclin D1 and cyclin A and the upregulation of cyclin B1. Later, G2/M arrest and deregulated microtubular networks were also found in methoxychalcone-treated SW620 colon cancer cells. synthesized several halogenated chalcones and their cell cycle analysis showed that the antiproliferative effect of the most potent compounds in HCT116 cells was associated with G2/M arrest and an increase in cells with sub-G0/G1 DNA content. The ability of chalcones to initiate cell cycle arrest at the G2/M phase has also been documented in numerous other publications.
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