In-vitro and In-vivo effects of Cu-Melo Seed´trypsinseed´trypsin Inhibitor on Angiogenesis and Tumor Characteristics in Balb-c Mice With Breast Cancer

BackgroundMelon seeds as an excellent supply of protease inhibitors may have a protective role against tumor progression and angiogenesis. However, its effects on angiogenesis and the mechanism of its motion on cancer progression remain elusive. This study aimed to investigate the effect of bioactive compounds of melon seed on the expression of angiogenesis genes in breast cancer cell lines.MethodsTrypsin inhibitor (TI) was purified from the seed powder of Cucumis Melo. Half-maximal inhibitory concentration (IC50) was determined for TI, extract of melon seed powder (EXT), and tamoxifen (TAM) by MTT test. Also, breast tumor was induced by subcutaneous injection of MC4-L2 cell line in blab-c inbreed mice breast tissue. After tumor growth, mice were treated with TI, EXT, and TAM to examine their effects on the tumor characteristics and the expression of the angiogenesis-related genes including MMP-2, MMP-9, and VEGF using the RT-PCR method.ResultsTI, EXT, TAM, and adjuvant treatment of TI+TAM resulted a reduction in expression of MMP-2, MMP-9, and VEGF. All treatments improved the breast tumor characteristics and the necrosis. The Real Time-PCR method verified the positive effects of the treatments on the breast cancer cell line and tumors.ConclusionThe results indicated that treatments with trypsin Inhibitor Purified from Cucumis Melo Seeds and also combination therapy of trypsin inhibitor and tamoxifen can be considered as an alternative therapy in breast cancer patients. Further studies are warranted.

Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming

Background Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions. However, the biological actions of adiponectin in cancer-specific lipid metabolism and its role in the regulation of cancer cell growth remain elusive. Methods The effects of adiponectin on fatty acid metabolism were evaluated by measuring the cellular neutral lipid pool, free fatty acid level, and fatty acid oxidation (FAO). Colocalization between fluorescent-labeled lipid droplets and LC3/lysosomes was employed to detect lipophagy activation. Cell viability and apoptosis were examined by MTS assay, caspase-3/7 activity measurement, TUNEL assay, and Annexin V binding assay. Gene expression was determined by real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The transcriptional activity of SREBP-1 was examined by a specific dsDNA binding assay. The modulatory roles of SIRT-1 and adiponectin-activated mediators were confirmed by gene silencing and/or using their pharmacological inhibitors. Observations from in vitro assays were further validated in an MDA-MB-231 orthotopic breast tumor model. Results Globular adiponectin (gAcrp) prominently decreased the cellular lipid pool in different breast cancer cells. The cellular lipid deficiency promoted apoptosis by causing disruption of lipid rafts and blocking raft-associated signal transduction. Mechanistically, dysregulated cellular lipid homeostasis by adiponectin was induced by two concerted actions: 1) suppression of fatty acid synthesis (FAS) through downregulation of SREBP-1 and FAS-related enzymes, and 2) stimulation of lipophagy-mediated lipolysis and FAO. Notably, SIRT-1 induction critically contributed to the adiponectin-induced metabolic alterations. Finally, fatty acid metabolic remodeling by adiponectin and the key role of SIRT-1 were confirmed in nude mice bearing breast tumor xenografts. Conclusion This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.

Breast Tumor Detection and Classification in Mammogram Images Using Modified YOLOv5 Network

Breast cancer incidence has been rising steadily during the past few decades. It is the second leading cause of death in women. If it is diagnosed early, there is a good possibility of recovery. Mammography is proven to be an excellent screening technique for breast tumor diagnosis, but its detection and classification in mammograms remain a significant challenge. Previous studies’ major limitation is an increase in false positive ratio (FPR) and false negative ratio (FNR), as well as a drop in Matthews correlation coefficient (MCC) value. A model that can lower FPR and FNR while increasing MCC value is required. To overcome prior research limitations, a modified network of YOLOv5 is used in this study to detect and classify breast tumors. Our research is conducted using publicly available datasets Curated Breast Imaging Subset of DDSM (CBIS-DDSM). The first step is to perform preprocessing, which includes image enhancing techniques and the removal of pectoral muscles and labels. The dataset is then annotated, augmented, and divided into 60% for training, 30% for validation, and 10% for testing. The experiment is then performed using a batch size of 8, a learning rate of 0.01, a momentum of 0.843, and an epoch value of 300. To evaluate the performance of our proposed model, our proposed model is compared with YOLOv3 and faster RCNN. The results show that our proposed model performs better than YOLOv3 and faster RCNN with 96% mAP, 93.50% MCC value, 96.50% accuracy, 0.04 FPR, and 0.03 FNR value. The results show that our suggested model successfully identifies and classifies breast tumors while also overcoming previous research limitations by lowering the FPR and FNR and boosting the MCC value.