Fitzpatrickfrom3969
Excessive use of diazinon, as an organophosphate pesticide (OP), contributes to cytotoxic and pathologic cellular damage and, in particular, oxidative stress. However, metal-oxide nanoparticles (NPs), such as cerium oxide (CeO2) and yttrium oxide (Y2O3), with the property of free radical scavenging demonstrated beneficial effects in the alleviation of oxidative stress biomarkers.
The aims of this study include evaluating beneficial effects of CeO2 NPs, Y2O3 NPs, and their combination against diazinon-induced oxidative stress in different tissues of brain, heart, lung, kidney, liver, and spleen.
Eight randomized groups of 6 adult male Wistar rats were formed. Each group of rats administered a different combination of diazinon, CeO2 and Y2O3 NPs daily and levels of oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation (LPO), total thiol molecules (TTM) and total anti-oxidant power (TAP) and catalase enzyme, were measured after 2 weeks of the treatment.
Measurements of the mhese nanoparticles reduce oxidative stress, it should be borne in the design of the study that additional doses of these substances reverse the beneficial effects.
Cinnamic acid (CA), also known as 3-phenyl-2-propenoic acid, is a naturally occurring aromatic fatty acid found commonly in cinnamon, grapes, tea, cocoa, spinach and celery. Various studies have identified CA to have anti-proliferative action on glioblastoma, melanoma, prostate and lung carcinoma cells.
Our objective was to investigate the molecular mechanism underlying the cytotoxic effect of CA in killing MDA-MB-231 triple negative breast cancer cells.
We performed MTT assay and trypan blue assay to determine cell viability and cell death, respectively. Comet analysis was carried out to investigate DNA damage of individual cells. Furthermore, AO/EtBr assay and sub-G1 analysis using flowcytometry was used to study apoptosis. Protein isolation followed by immunoblotting was used to observe protein abundance in treated and untreated cancer cells.
Using MTT assay we have determined CA to reduce cell viability in MDA-MB-231 breast cancer cells and tumorigenic HEK 293 cells but not in normal NIH3T3 fibroblast cells. Subsequently, trypan blue assay and comet assay showed CA to cause cell death and DNA damage, respectively, in the MDA-MB-231 cells. Using AO/EtBr staining and sub-G1 analysis we further established CA to increase apoptosis. Additionally, immunoblotting showed the abundance of TNFA, TNF receptor 1 (TNFR1) and cleaved caspase-8/-3 pro-apoptotic proteins to increase on CA treatment. Subsequently, blocking of TNFA-TNFR1 signalling by small molecule inhibitor, R-7050, reduced the expression of cleaved caspase-8 and caspase-3 at the protein level.
Thus, from the above observations we can conclude that CA is an effective anticancer agent that can induce apoptosis in breast cancer cells via TNFA-TNFR1 mediated extrinsic apoptotic pathway.
Thus, from the above observations we can conclude that CA is an effective anticancer agent that can induce apoptosis in breast cancer cells via TNFA-TNFR1 mediated extrinsic apoptotic pathway.
Cancer is a life-threatening group of diseases and universally the second main cause of death. Design and development of new scaffolds targeting selective cancer cells is considered a promising goal for cancer treatment.
Chalcone derivatives; 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolone, were previously prepared and evaluated against the oral cavity squamous cell carcinoma cell line, HSC-2, and were reported to have remarkably high tumor selectivity. The aim of this study is to further investigate the anticancer activities of the chalcone derivatives against human colon cancer cells with possible elucidation of their mechanism of action.
Computational studies were conducted to explore the potential interaction of the synthesized molecules with the phosphatidylinositol-4,5-bisphosphate 3-kinaseα (PI3Kα). Biological evaluation of the antiproliferative activities associated with compounds 1-23 was carried out against the colon cancer cell line HCT116. Lactate dehydrogenase (LDH) activity was measured to study necrosis while the caspase-3 activation and DNA measurements were used to evaluate apoptosis in the treated cells.
Glide studies against PI3Kα kinase domain demonstrated that the 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolone scaffold forms H-bond with K802, Y836, E849, V851, N853, Q859, and D933, and it fits the fingerprint of PI3Kα active inhibitors. Biological evaluation of the reported compounds in HCT116 cell line confirmed that the series inhibited PI3Kα activity and induced apoptosis via activation of caspase-3 and reduction of DNA content.
The recently developed compounds might be employed as lead structures for the design of new antitumor drugs targeting PI3Kα.
The recently developed compounds might be employed as lead structures for the design of new antitumor drugs targeting PI3Kα.
Triple Negative Breast Cancer (TNBC) is an aggressive and highly heterogeneous subtype of breast cancer associated with poor prognosis. A better understanding of the biology of this complex cancer is needed to develop novel therapeutic strategies for the improvement of patient survival. We have previously demonstrated that Thymoquinone (TQ), the major phenolic compound found in Nigella sativa, induces anti-proliferative and anti-metastatic effects and inhibits in vivo tumor growth in orthotopic TNBC models in mice. see more Also, we have previously shown that Beclin-1 and LC3 autophagy genes contributes to TNBC cell proliferation, migration and invasion, suggesting that Beclin-1 and LC3 genes provide proto-oncogenic effects in TNBC. However, the role of Beclin-1 and LC3 in mediating TQ-induced anti-tumor effects in TNBC is not known.
To investigate the effects of TQ on the major autophagy mediators, Beclin-1 and LC3 expression, as well as autophagic activity in TNBC cells.
Cell proliferation, colony formation, mlated to cell migration/invasion and angiogenesis, including Integrin-β1, VEGF, MMP-2 and MMP- 9, suggesting that TQ may be used to control autophagic activity and oncogenic signaling in TNBC.
