ABSTRACT
Delphinidin is a major anthocyanidin compound found in various fruits. It has anti-inflammatory, anti-oxidant, and various other biological activities. In this study, we identified the epigenetic modulators that mediate the apoptotic effect of delphinidin in human prostate cancer cells. We found that treatment of LNCaP cells (a p53 wild-type, human prostate cancer cell line) with delphinidin increased caspase-3, -7, and -8 activity, whereas it decreased histone deacetylase activity. Among class I HDACs, the activity of HDAC3 was specifically inhibited by delphinidin. Moreover, the induction of apoptosis by delphinidin was dependent on caspase-mediated cleavage of HDAC3, which results in the acetylation and stabilization of p53. We also observed that delphinidin potently upregulated pro-apoptotic genes that are positively regulated by p53, and downregulated various anti-apoptotic genes. Taken together, these results show that delphinidin induces p53-mediated apoptosis by suppressing HDAC activity and activating p53 acetylation in human prostate cancer LNCaP cells. Therefore, delphinidin may be useful in the prevention of prostate cancer.
Subject(s)
Anthocyanins/pharmacology , Apoptosis , Histone Deacetylases/metabolism , Prostatic Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Acetylation , Antineoplastic Agents, Phytogenic/pharmacology , Caspase 3/metabolism , Caspase 7/metabolism , Caspase 8/metabolism , Cell Line, Tumor , Cell Survival , Epigenesis, Genetic , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Histone Deacetylases/genetics , Humans , Male , Plant Extracts/pharmacology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , RNA Interference , Tumor Suppressor Protein p53/geneticsABSTRACT
Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536].
Subject(s)
Caspase Inhibitors/pharmacology , Caspases/metabolism , Lizards , Protein Kinase Inhibitors/pharmacology , Proteins/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Urinary Bladder Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Drugs, Chinese Herbal , Humans , Isoenzymes , Proto-Oncogene Proteins c-akt/metabolism , Urinary Bladder Neoplasms/enzymology , Urinary Bladder Neoplasms/pathologyABSTRACT
To find acetylcholinesterase (AChE) inhibitors for the prevention of neurological disorders, such as Alzheimer's disease, ethanol extracts of promising traditional edible Korean plants were tested. Among them, Rubus coreanus Miquel extract exhibited the most significant AChE inhibitory activity. The effect of R. coreanus extract on trimethyltin-induced memory impairment in mice was investigated using Y-maze and passive avoidance tests. Our results showed that administration of R. coreanus extract significantly improved alternation behavior and step-through latency. In addition, R. coreanus extract was sequentially fractionated, and the purified constituent was determined to be 3,4,5-trihydroxybenzoic acid.
Subject(s)
Cholinesterase Inhibitors/administration & dosage , Cognition Disorders/prevention & control , Dementia/drug therapy , Plant Extracts/administration & dosage , Rosaceae/chemistry , Acetylcholinesterase/metabolism , Animals , Cholinesterase Inhibitors/chemistry , Cognition Disorders/drug therapy , Cognition Disorders/enzymology , Cognition Disorders/psychology , Dementia/enzymology , Dementia/psychology , Disease Models, Animal , Humans , Male , Maze Learning , Mice , Mice, Inbred ICR , Phytotherapy , Plant Extracts/chemistryABSTRACT
The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide (Abeta). Abeta is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxi-dation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on Abeta-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2,7 -dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by reducing oxidative stress.
Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Antioxidants/pharmacology , Gardenia/chemistry , Plant Extracts/pharmacology , Animals , Avoidance Learning/drug effects , Cell Death/drug effects , Male , Memory/drug effects , Mice , Neurons/drug effects , PC12 Cells , Palmitic Acid/pharmacology , Rats , Spatial Behavior/drug effectsABSTRACT
This study's objective was to clarify the ameliorative effects ferulic acid (4-hydroxy-3-methoxycinnamic acid) has against cognitive deficits and ChAT activation in trimethyltin (TMT) induced, memory injured mice following a 28-d ferulic acid treatment. After administering TMT for 3 d, each mouse performed Y-maze and passive avoidance tests to check immediate working memory performance and cognitive function. The results showed that ferulic acid administration attenuated TMT-induced memory injury and a decline in ChAT activity in the mice. This suggests that ferulic acid might be useful for preventing cognitive dysfunction as well as for boosting the activation of ChAT in dementia.
Subject(s)
Cognition Disorders/chemically induced , Cognition Disorders/prevention & control , Coumaric Acids/pharmacology , Free Radical Scavengers/pharmacology , Trimethyltin Compounds/antagonists & inhibitors , Trimethyltin Compounds/toxicity , Animals , Avoidance Learning/drug effects , Brain/drug effects , Brain/enzymology , Choline O-Acetyltransferase/metabolism , Cognition Disorders/psychology , Male , Memory/drug effects , Mice , Mice, Inbred ICRABSTRACT
Of 30 herbal plants tested, the methanol extracts of Eucommia ulmoides (52%), Evodia officinalis (45%), and Pleuropterus multiflorus (41%) each showed a potent inhibitory effect on the matrix metalloproteinase-1 (MMP-1) production in ultraviolet B (UVB)-irradiated human fibroblasts. Aucubin was isolated as the MMP-1 inhibitor from E. ulmoides, and significantly suppressed the production of MMP-1 by nearly 57% compared to the control. It also reduced MMP-1 mRNA expression. These results suggest that aucubin is a photoprotective phytochemical, and could be used as a potential agent in preventing photoaging.