Research on the Enhancement Mechanism of Dihydromyricetin on the Inhibitory Role of Cisplatin Towards Breast Cancer Cell Activity

Objective: The purpose of our study was to evaluate Enhancement Mechanism of Dihydromyricetin (DMY) on the Inhibitory Role of Cisplatin Towards Breast Cancer Cell Activity. Materials and Methods: The MCF-7 were divided into NC, DMY, Cis and DMY+Cis groups. Using relative methods (MTT, TUNEL, Transwell, flow cytometry and wound healing) to evaluate MCF-7 cell biological activities including cell viability, apoptosis, invasion cell number and wound healing rate. The relative proteins expressions including FOXO-1, Noxa, Bim, Cyto C, Caspase-3, Caspase-9 and Apaf-1 were evaluated by WB assay. Results: MCF-7 cell viability, invasion cell number and wound healing rates were significantly depressed and apoptosis rate were significantly increased in DMY, Cis and DMY+Cis groups (P < 0.01, respectively). Compared with Cis group, cell viability, invasion cell number and wound healing rates were significantly depressed and apoptosis rate were significantly increased in DMY+Cis group (P < 0.05, respectively). Conclusion: Dihydromyricetin can effectively enhance the inhibitory effect of cisplatin on breast cancer cells.

Cold Atmospheric Plasma Attenuates Breast Cancer Cell Growth Through Regulation of Cell Microenvironment Effectors

Breast cancer exists in multiple subtypes some of which still lack a targeted and effective therapy. Cold atmospheric plasma (CAP) has been proposed as an emerging anti-cancer treatment modality. In this study, we investigated the effects of direct and indirect CAP treatment driven by the advantageous nanosecond pulsed discharge on breast cancer cells of different malignant phenotypes and estrogen receptor (ER) status, a major factor in the prognosis and therapeutic management of breast cancer. The main CAP reactive species in liquid (i.e. H2O2, NO2−/NO3−) and gas phase were determined as a function of plasma operational parameters (i.e. treatment time, pulse voltage and frequency), while pre-treatment with the ROS scavenger NAC revealed the impact of ROS in the treatment. CAP treatment induced intense phenotypic changes and apoptosis in both ER+ and ER- cells, which is associated with the mitochondrial pathway as evidenced by the increased Bax/Bcl-2 ratio and cleavage of PARP-1. Interestingly, CAP significantly reduced CD44 protein expression (a major cancer stem cell marker and matrix receptor), while differentially affected the expression of proteases and inflammatory mediators. Collectively, the findings of the present study suggest that CAP suppresses breast cancer cell growth and regulates several effectors of the tumor microenvironment and thus it could represent an efficient therapeutic approach for distinct breast cancer subtypes.

miR-641 Inhibited Cell Proliferation and Induced Apoptosis by Targeting NUCKS1/PI3K/AKT Signaling Pathway in Breast Cancer

Objective. Studies revealed an important role of microRNAs (miRNAs) in multiple cancers, including breast cancer. In the present study, we evaluated the role and function of miR-641 in breast cancer. Methods. The expression level of miR-641 in breast cancer cell lines (Hs-578T, MCF7, HCC1937, and MAD-MB-231) was determined by real-time PCR. Functional analyses, including CCK-8 assay, transwell assay, wound-healing assay, and apoptosis detection, were carried out to explore the roles of miRNA-641 in malignant behaviors of breast cancer. Luciferase report assay was used to investigate the regulatory association of miRNA-641 with its potential targets. Results. The expression levels of miR-641 were downregulated, while the expression levels of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were increased in breast cancer cell lines. The in vitro results showed that miR-641 repressed proliferation and migration/invasion and promoted apoptosis of breast cancer cells. NUCKS1, a positive regulator of phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) pathway, was confirmed as a direct target of miR-641. The of treatment of the PI3K agonist, 740Y-P, could abrogate the antioncogenic potentials of miR-641 in breast cancer cells. Conclusion. miR-641 functioned as a tumor suppressor through the PI3K/AKT signaling pathway via targeting NUCKS1 in breast cancer.

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.

Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 μM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triple-negative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.