[Inhibition of the expression of prostate specific antigen by curcumin].
ABSTRACT To study the effect of curcumin on the expression of prostate specific antigen (PSA).
AXSYM system-chemical luciferase method was used to examine the content of PSA in prostate cancer cell lines, LNCap after treated with different doses of curcumin. pGL3-PSA luciferase expression vector, containing 640 bp DNA of PSA gene 5' promoter region was constructed and transfected into LNCap cell with lipofectin. Through detecting the activity of luciferase, the effect of curcumin on the promoter of PSA was studied. Western blotting was used to detect expression of androgen receptor (AR) in LNCap cell with different concentrations of curcumin.
The expression of PSA was inhibited and activity of luciferase was reduced by curcumin. There was also significant difference in AR expression as shown by Western blotting experiment after treatment of different doses of curcumin.
Through inhibiting AR expression, curcumin reduced the function of PSA promoter and inhibited PSA protein expression.
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ABSTRACT: Based on unique biology of prostate cancer, prostate-specific antigen could be a useful target for prostate cancer therapies. Such targeting requires the identification of highly selective inhibitor-binding sites. Three-dimensional structure was calculated by homology modeling. The overall structure of human prostate-specific antigen is composed of two beta-barrel domain, kallikrein loop and active-site triad His57, Asp102, and Ser195. Structure of human prostate-specific antigen is quite similar to hK-1 and HPK-3. The major differences were observed at kallikrein loop and position of active site. The substrate-binding pocket is predominated by hydrophobic residues and the bottom of the specificity pocket contains Ser189 as in chymotrypsin, which provides substrate specificity. The hydrophobic, and preferentially aromatic (Trp215), amino acid residues are determinant of substrate binding due to the presence of hydrophobic crevice between Tyr99 and Trp215. Crystal structure of human prostate-specific antigen is not determined till now and hence the report on an accurate and comparative model of human prostate-specific antigen is probably to help in understanding their functional network and finally could be helpful in structure-based rational drug designing.Chemical Biology & Drug Design 10/2007; 70(3):261-7. · 2.47 Impact Factor
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ABSTRACT: Individuals over 80 years of age represent the most rapidly growing segment of the population, and late-life dementia has become a major public health concern worldwide. Development of effective preventive and treatment strategies for late-life dementia relies on a deep understanding of all the processes involved. In the centuries since the Greek philosopher Pythagoras described the inevitable loss of higher cognitive functions with advanced age, various theories regarding the potential culprits have dominated the field, ranging from demonic possession, through 'hardening of blood vessels', to Alzheimer disease (AD). Recent studies suggest that atrophy in the cortex and hippocampus-now considered to be the best determinant of cognitive decline with aging-results from a combination of AD pathology, inflammation, Lewy bodies, and vascular lesions. A specific constellation of genetic and environmental factors (including apolipoprotein E genotype, obesity, diabetes, hypertension, head trauma, systemic illnesses, and obstructive sleep apnea) contributes to late-life brain atrophy and dementia in each individual. Only a small percentage of people beyond the age of 80 years have 'pure AD' or 'pure vascular dementia'. These concepts, formulated as the dynamic polygon hypothesis, have major implications for clinical trials, as any given drug might not be ideal for all elderly people with dementia.Nature Reviews Neurology 11/2009; 5(12):649-58. · 15.52 Impact Factor