Snail protein inhibition by drug repositioning for recurrent breast cancer: an in-silico study

Objective: Snail is a transcription factor that promotes epithelial-mesenchymal transition (EMT) and facilitates tumor progression and metastasis in breast cancer. Therefore, it is a promising target for the development of anticancer agents. The objective of this study was to identify FDA-approved drugs that can be repurposed as Snail inhibitors. Materials and Methods: Using a virtual screening strategy, three molecules were selected among 1615 (Stivarga, Paritaprevir and Sorafenib). Molecular docking and molecular dynamics simulation were performed to examine Snail-drugs interactions. Results: Our docking analysis identified Stivarga and Sorafenib, two antineoplastic drugs, as potential repositioning drugs to treat recurrent breast cancer due to their low free binding energy values. Additional molecular dynamics simulations of the Snail-drug systems revealed that Sorafenib was the most stable, lasting from 30 to 120 ns and forming 2-4 hydrogen bonds. Conclusions: The antineoplastic drugs Stivarga and Sorafenib have better affinity and inhibition of Snail and could be a simple drug therapy for recurrent breast cancer

Antidiabetic treatment, obesity, and cancer risk in Algerian patients with type 2 diabetes mellitus

OBJECTIVE: Several studies have shown that antidiabetic drugs and obesity can modulate the risk of developing cancer. The objective of this study was to assess the impact of the use of antidiabetic drugs and obesity on the risk of developing cancers in type 2 diabetics. MATERIALS AND METHODS: Data for 1220 patients were collected from the processing of files and a pre-established questionnaire. The anthropobiological parameters and the associated treatment type have been unspecified. RESULTS: Women (OR=17.26; 95% CI=2.88-103.45, p<0.01), overweight individuals (OR=4.81; 95% CI=1.63-14.14, p<0.01) and hypertensive diabetic subjects (OR=3.82; 95% CI=1.39-10.49, p< 0.01) are more exposed to cancers. It is interesting to note that diabetic subjects treated with insulin have a reduced risk of developing cancer (OR=0.22; 95% CI=0.07-0.67, p<0.01). Diabetic subjects treated with metformin have a four and a half times higher risk of developing cancer (OR=4.61; 95% CI=1.48-14.37, p<0.01). CONCLUSIONS: In type 2 diabetic subjects, cancer is significantly linked to overweight, to the presence of essential hypertension in individuals under hypotensive as well as in patients treated with metformin

Assessment of acute and sub-acute toxicity of olive pomace in female Wistar rats

Objective: Olive Pomace (OP) is considered to be a rich source of phenolic compounds. Recently many researches showed a broad biological activity of this by-product of the olive oil production process in addition to their emergence as value-added materials with potential applications in the pharmaceutical, food, and nutraceutical industries. The present study is aimed to evaluate in vivo toxicological activities of OP. Materials and Methods: The qualitative phytochemical analysis aims to determine the key phytoconstituents found in OP. For the in vivo study, two types of tests are performed: acute and 28-day repeated oral toxicity studies in Wistar rats for evaluation of hematological, biochemical, and histological parameters. Results: The qualitative phytochemical analysis has revealed the presence of polyphenols, flavonoids, tannins, saponins, quinones, anthraquinones, terpenoids, and compounds reduced in our methanol extract of OP. In acute oral toxicity, no treatment-related death or toxic signs are observed in female rats for 14 days in 200, 2000, 3000, and 5000 mg/kg doses, besides LD50 value is found to be up to 2000 mg/kg bodyweight. As for the Globally Harmonized System of Classification and Labelling of Chemicals. 28-days sub-acute toxicity study is carried in female rats at four dose levels (3.12, 31.25, 125 and 500 mg/kg), no changes in observation related death and toxic signs when compared with control. The hematological and biochemical investigation shows a significant change (p>0.05) in the high-level doses (500 mg/kg). Conclusions: According to the findings of this study, OP extract has the potential to be used to generate new anti-cancer and antioxidant additives for pharmaceutical and food manufacturing. Long-term in vivo toxicological tests should also be conducted to determine a safe dosage of OP extract