In vitro and in silico studies for the identification of anti-cancer and antibacterial peptides from camel milk protein hydrolysates.

Today, breast cancer and infectious diseases are very worrying that led to a widespread effort by researchers to discover natural remedies with no side effects to fight them. In the present study, we isolated camel milk protein fractions, casein and whey proteins, and hydrolyzed them using pepsin, trypsin, and both enzymes. Screening of peptides with anti-breast cancer and antibacterial activity against pathogens was performed. Peptides derived from whey protein fraction with the use of both enzymes showed very good activity against MCF-7 breast cancer with cell viability of 7.13%. The separate use of trypsin and pepsin to digest whey protein fraction yielded peptides with high antibacterial activity against S. aureus (inhibition zone of 4.17 ± 0.30 and 4.23 ± 0.32 cm, respectively) and E. coli (inhibition zone of 4.03 ± 0.15 and 4.03 ± 0.05 cm, respectively). Notably, in order to identify the effective peptides in camel milk, its protein sequences were retrieved and enzymatically digested in silico. Peptides that showed both anticancer and antibacterial properties and the highest stability in intestinal conditions were selected for the next step. Molecular interaction analysis was performed on specific receptors associated with breast cancer and/or antibacterial activity using molecular docking. The results showed that P3 (WNHIKRYF) and P5 (WSVGH) peptides had low binding energy and inhibition constant so that they specifically occupied active sites of protein targets. Our results introduced two peptide-drug candidates and new natural food additive that can be delivered to further animal and clinical trials.

Identification of hub pathways and drug candidates in gastric cancer through systems biology.

Gastric cancer is the fourth cause of cancer death globally, and gastric adenocarcinoma is its most common type. Efforts for the treatment of gastric cancer have increased its median survival rate by only seven months. Due to the relatively low response of gastric cancer to surgery and adjuvant therapy, as well as the complex role of risk factors in its incidences, such as protein-pomp inhibitors (PPIs) and viral and bacterial infections, we aimed to study the pathological pathways involved in gastric cancer development and investigate possible medications by systems biology and bioinformatics tools. In this study, the protein-protein interaction network was analyzed based on microarray data, and possible effective compounds were discovered. Non-coding RNA versus coding RNA interaction network and gene-disease network were also reconstructed to better understand the underlying mechanisms. It was found that compounds such as amiloride, imatinib, omeprazole, troglitazone, pantoprazole, and fostamatinib might be effective in gastric cancer treatment. In a gene-disease network, it was indicated that diseases such as liver carcinoma, breast carcinoma, liver fibrosis, prostate cancer, ovarian carcinoma, and lung cancer were correlated with gastric adenocarcinoma through specific genes, including hgf, mt2a, mmp2, fbn1, col1a1, and col1a2. It was shown that signaling pathways such as cell cycle, cell division, and extracellular matrix organization were overexpressed, while digestion and ion transport pathways were underexpressed. Based on a multilevel systems biology analysis, hub genes in gastric adenocarcinoma showed participation in the pathways such as focal adhesion, platelet activation, gastric acid secretion, HPV infection, and cell cycle. PPIs are hypothesized to have a therapeutic effect on patients with gastric cancer. Fostamatinib seems a potential therapeutic drug in gastric cancer due to its inhibitory effect on two survival genes. However, these findings should be confirmed through experimental investigations.