Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FLZ is a synthetic novel squamosamide derivative and has previously been proved to be a potential drug for Parkinson's disease and Alzheimer's disease. FLZ has strong antioxidant activity, which implies that FLZ could eliminate excessive intracellular reactive oxygen species (ROS) in tumor cells and induce a pathway related to low cellular ROS levels, thereby inhibiting tumor cells proliferation. However, few reports have focused on the antitumor effects of FLZ. In this study, we investigated the antitumor efficacy of FLZ in HepG2 cells and the mechanism of cell growth inhibition. FLZ effectively inhibited HepG2 cell proliferation in a dose- and time-dependent manner; meanwhile, it was minimally toxic to normal cells. FLZ induced a significant decrease in oxidative stress through elimination of excessive intracellular ROS and strengthening of the glutathione antioxidant system. In addition, FLZ can effectively attenuate redundant [Ca(2+)](i), thereby avoiding uncontrolled amplification by Ca(2+)/ROS positive feedback. Furthermore, Western blot showed that FLZ inhibited phosphorylation of Akt and retinoblastoma protein (Rb), down-regulated the expressions of cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), and enhanced the expression of CDK inhibitor p27(kip1), while did not affect CDK4 expression. These results suggest that FLZ has potent anti-proliferative activity against malignant human hepatoma cells via modulation of the expression or activation of cell-cycle regulatory proteins, which are associated with decreased Ca(2+)/ROS levels, and indicate that FLZ is a potential liver cancer drug worthy of further research and development.
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PMID:Anti-proliferative effects of the novel squamosamide derivative (FLZ) on HepG2 human hepatoma cells by regulating the cell cycle-related proteins are associated with decreased Ca(2+)/ROS levels. 2183 69

The recognition that G(1)/S checkpoint dysfunctions in Alzheimer's disease (AD) has opened a novel avenue for better understanding the pathogenesis of AD, as well as for searching for new biomarkers for early diagnosis of AD. In present study, we investigated Cyclin E, Rb, CDK2 and E(2)F-1, four G1/S checkpoint proteins, in the lymphocytes from AD and non-AD individuals, and explored their potential for diagnosis application. A total of 176 age-matched subjects were enrolled, including 74 AD patients, 80 cognitively normal individuals, 11 patients with Parkinson's disease (PD) and 11 patients with vascular dementia (VaD). Peripheral blood lymphocytes were collected from each individual, and Cyclin E, Rb, CDK2, E(2)F-1 were analyzed by enzyme-linked immunosorbent assay, western blot, confocal microscopy and flow cytometry. The results showed that four proteins increased in AD compared with other three groups (P<0.05), with CDK2 and E(2)F-1 showing higher statistical significance (P<0.01). Their specificity/sensitivity (Cyclin E 84%/81%; Rb 74%/89%, CDK2 80%/78%, E(2)F-1 85%/85%) were acceptable, suggesting their potential as biomarkers for AD. Furthermore, these four proteins had the best sensitivity/specificity and highest Area Under the Curve (AUC) in mild-moderate AD compared with the severe AD.
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PMID:G1/S checkpoint proteins in peripheral blood lymphocytes are potentially diagnostic biomarkers for Alzheimer's disease. 2292 16


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