Targeting Colorectal Cancer Cells with a Functionalised Calix[4]arene Receptor: Biophysical Studies

Colorectal cancer (CRC) is a disease which is causing a high degree of mortality around the world. The present study reports the antiproliferative impact of the thioacetamide calix[4]arene, CAII receptor on a highly differentiated Caco-2 cell line. This statement is corroborated by the MTT assay results which revealed a reduction in the cell viability with an IC50 value of 19.02 ± 0.04 µM. Microscopic results indicated that at the starting amount of 10 µM of CAII, a decrease in cells confluency can already be observed in addition to changes in cells morphology. Cell metabolic pathway changes were also investigated. 1H NMR findings showed downregulation in lactate, pyruvate, phosphocholine, lipids, and hydroxybutyrate with the upregulation of succinate, indicating a decline in the cells proliferation. Some biochemical alterations in the cells as a result of the CAII treatment were found by Raman spectroscopy.

Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance

Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5′-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes.

Saponins as a Potential PFN2 Inhibitor: In silico Approach

Colorectal cancer (CRC) disease has a high mortality rate and has recently involved human profilin II (Pfn2), an actin-binding protein, as a promoter of its invasiveness and progression. This work evaluated the binding affinity of oleanolic acid saponin over Pfn2 and its structural stability. QM and MM techniques were applied to perform geometrical optimization and calculation of the reactive sites from oleanolic acid, whereas molecular docking and MD simulations for protein-ligand interaction under physiological conditions. Oleanolic acid saponin showed a high binding affinity to the Pfn2 PLPbinding site. Analysis of the protein-ligand structure suggests saponin as a molecule with high potential for developing new drugs against Pfn2 in colorectal cancer cells.