Computational Approaches for Cancer-Fighting: From Gene Expression to Functional Foods

Abstract

It is today widely accepted that a healthy diet is very useful to prevent the risk for cancer or its deleterious effects. Nutrigenomics studies are therefore taking place with the aim to test the effects of nutrients at molecular level and contribute to the search for anti-cancer treatments. These efforts are expanding the precious source of information necessary for the selection of natural compounds useful for the design of novel drugs or functional foods. Here we present a computational study to select new candidate compounds that could play a role in cancer prevention and care. Starting from a dataset of genes that are co-expressed in programmed cell death experiments, we investigated on nutrigenomics treatments inducing apoptosis, and searched for compounds that determine the same expression pattern. Subsequently, we selected cancer types where the genes showed an opposite expression pattern and we confirmed that the apoptotic/nutrigenomics expression trend had a significant positive survival in cancer-affected patients. Furthermore, we considered the functional interactors of the genes as defined by public protein-protein interaction data, and inferred on their involvement in cancers and/or in programmed cell death. We identified 7 genes and, from available nutrigenomics experiments, 6 compounds effective on their expression. These 6 compounds were exploited to identify, by ligand-based virtual screening, additional molecules with similar structure. We checked for ADME criteria and selected 23 natural compounds representing suitable candidates for further testing their efficacy in apoptosis induction. Due to their presence in natural resources, novel drugs and/or the design of functional foods are conceivable from the presented results.

Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles

“…The early symptoms of this cancer are very subtle or lacking, so it is often diagnosed after the disease has deteriorated significantly, which makes the early diagnosis rate only 1.43%. With the development of bioinformatics, transcriptomic studies have found that some genes involved in tumorigenesis and metastasis are differentially expressed in tumor and normal tissues [72][73][74][75]. This opens the possibility for early detection of esophageal squamous cell carcinoma.…”

Cyclocarbonylation of Allenyl Glyoxylate Strategy to Build the Tricyclic Core of Cyclocalopin A

“…* sı Supporting Information ABSTRACT: An approach for the construction of the tricyclic framework of naturally occurring cyclocalopin A is described. The establishment of the crucial intermediate α-methylene bis-γ,δlactone involves a [2 + 2 + 1]-cyclocarbonylation of newly introduced allenyl glyoxylate via direct methods using Mo(CO) 6 or sequential reaction pathways. The sequential reaction route involved a stannylative cyclization by Pd(0) catalyst, bromination of an vinyl stannane moiety, and final cyclocarbonylation by palladium catalysis to provide the bis-γ,δ-lactone.…”

“…Cyclocalopin shows potent free-radicalscavenging activity against superoxide, DPPH, and ABTS radicals with IC 50 values of 1.2−5.4 μg/mL and recently anticancer activities against several cell lines. 4,6 More than 20 types of cyclocalopin families have been discovered, with diverse structures such as cyclocalopin A (fused bicyclic with spiro-ring), cyclocalopin E (fused and bridged four rings), and isocyclocalopin A (bridged bicyclic rings with spiro-unit). Nonetheless, all cyclocalopin family natural products were closely related each other by simple chemical and biological conversions as described in Scheme 1.…”

“…As shown in Scheme , cyclocalopin A is a highly oxygenated compound consisting of a fused and a spiro-ring system. Cyclocalopin shows potent free-radical-scavenging activity against superoxide, DPPH, and ABTS radicals with IC 50 values of 1.2–5.4 μg/mL and recently anticancer activities against several cell lines. , …”