Modulatory Effect of Chlorogenic Acid and Coffee Extracts on Wnt/ß-Catenin Pathway in Colorectal Cancer Cells.

The Wnt/ß-Catenin pathway alterations present in colorectal cancer (CRC) are of special interest in the development of new therapeutic strategies to impact carcinogenesis and the progression of CRC. In this context, different polyphenols present in natural products have been reported to have modulatory effects against the Wnt pathway in CRC. In this study, we evaluate the effect of two polyphenol-rich coffee extracts and chlorogenic acid (CGA) against SW480 and HT-29 CRC cells. This involved the use of MTT and SRB techniques for cell viability; wound healing and invasion assay for the evaluation of the migration and invasion process; T cell factor (TCF) reporter plasmid for the evaluation of transciption factor (TCF) transcriptional activity; polymerase chain reaction (PCR) of target genes and confocal fluorescence microscopy for ß-Catenin and E-Cadherin protein fluorescence levels; and subcellular localization. Our results showed a potential modulatory effect of the Wnt pathway on CRC cells, and we observed a reduction in the transcriptional activity of ß-catenin. All the results were prominent in SW480 cells, where the Wnt pathway deregulation has more relevance and implies a constitutive activation of the signaling pathway. These results establish a starting point for the discovery of a mechanism of action associated with these effects and corroborate the anticancer potential of polyphenols present in coffee, which could be explored as chemopreventive molecules or as adjunctive therapy in CRC.

Modulation of the Canonical Wnt Signaling Pathway by Dietary Polyphenols, an Opportunity for Colorectal Cancer Chemoprevention and Treatment.

In the last few decades there has been a rise in the worldwide incidence of colorectal cancer which can be traced back to the influence of well-known modifiable risk factors such as lifestyle, diet and obesity. Conversely, the consumption of fruits, vegetables and fiber decreases the risk of CRC, which is why dietary polyphenols have aroused interest in recent years as potentially anti-carcinogenic compounds. One of the driving forces of colorectal carcinogenesis, in both sporadic and hereditary CRC, is the aberrant activation/regulation of the Wnt/ß-catenin pathway. This review discusses reports of modulation of the Wnt/ß-Catenin signaling pathway by dietary polyphenols (resveratrol, avenanthramides, epigallocatechinin, curcumin, quercetin, silibinin, genistein and mangiferin) specifically focusing on CRC, and proposes a model as to how this modulation occurs. There is potential for implementing these dietary polyphenols into preventative and therapeutic therapies for CRC as evidenced by some clinical trials that have been carried out with promising results.

Biological Impact of Phenolic Compounds from Coffee on Colorectal Cancer.

Colorectal cancer is one of the leading death-related diseases worldwide, usually induced by a multifactorial and complex process, including genetic and epigenetic abnormalities and the impact of diet and lifestyle. In the present study, we evaluated the biological impact of two of the main coffee polyphenols, chlorogenic acid (CGA) and caffeic acid (CA), as well as two polyphenol-rich coffee extracts (green coffee extract and toasted coffee Extract) against SW480 and SW620 colorectal cancer cells. First, the total phenolic content and the antioxidant capability of the extracts were determined. Then, cytotoxicity was evaluated by MTT and SBR. Finally, a wound healing assay was performed to determine the impact on the cell migration process. The results showed a cytotoxic effect of all treatments in a time and dose-dependent manner, which decreased the viability in both cell lines at 24 h and 48 h; likewise, the migration capability of cells decreased with low doses of treatments. These results suggest the potential of coffee to modulate biological mechanisms involved in colorectal cancer development; however, more studies are required to understand the mechanistic insights of these observations.

Ruthenium Complex Induce Cell Death in G-415 Gallbladder Cancer Cells.

PURPOSE: In this work, we present a recently developed ruthenium complex that shows anticancer activity in gallbladder cancer cells. METHODS: After the synthesis of the new ruthenium complexes, the antiproliferative, cytotoxicity, and apoptosis activities were evaluated in vitro by the triple assay ApoTox-Glo. Then, the transcription levels of genes related to apoptosis were evaluated by real-time PCR (q-PCR). RESULTS: The ruthenium complex, called Ru-UCN3, inhibits the proliferation of gallbladder cancer cells G-415 by means of apoptosis, which was demonstrated by the overexpression of the pro-apoptotic genes Puma, Diablo, and Caspasa-9 together with the repression of the anti-apoptotic genes Bcl-xL and Bcl-2. In addition, we found strong caspase 3/7 activity in the cells at 24 h of the Ru-UCN3 exposure, which was evaluated by the triple ApoTox-Glo assay. CONCLUSION: The new ruthenium complexes evaluated had an inhibitory effect on G-415 cells. We think that Ru-UCN3 could be a promising anticancer agent, which should be explored with more in vitro and in vivo assays and probably with the chemical modulation of this molecule.