To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

500 pmol/L were greater than those in any group.Conclusion Serum MMP-2 can be involved in left ventricular remodeling of HF,and measuring its concentration is helpful to judge the severity and prognosis of HF.

OBJECTIVETo study the content of phytoestrogen in dissimilarity herbs.

METHODThe activity of phytoestrogen in heat-clearing drugs, drugs for relieving exterior syndrome, diuretic, anastaltics, tonics and astringents were detected based on the recombinant yeast cell (W303-1A/hER-ERE-Lac Z). The estrogenic activity in traditional Chinese materia medica were assayed quantitatively by determining the expression of beta-galactosidase.

RESULTThe phytoestrogen concentration (6.35 x 10(-3) nmol x g(-1) E2 equivalent) in heat-clearing drugs was the highest while that in anastaltic and tonic drugs was the lowest, which was less than the detected limit.

CONCLUSIONCompared with the other traditional Chinese materia medica, the content of phytoestrogen, which can bind to estrogen receptor, in giant knotweed rhizome, forsythia suspense, ash bark, baical skullcap root and ophiopogonis tuber were higher.

Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Phytoestrogens ; analysis ; metabolism ; Plants, Medicinal ; chemistry ; Receptors, Estrogen ; metabolism ; Recombination, Genetic ; Saccharomyces cerevisiae ; chemistry ; cytology ; drug effects ; genetics ; beta-Galactosidase ; analysis

Not Abstract.

OBJECTIVETo investigate the effect of arctiin on advanced oxidation protein product (AOPP)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells and explore the mechanisms underlying this effect.

METHODSHuman proximal tubular cells (HK-2 cells) were treated with bovine serum albumin (BSA) or AOPPs in the presence or absence of arctiin. The expressions of E-cadherin, vimentin, and GRP78 at the protein and mRNA levels in the cells were examined using Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry with DCFH-DA as the fluorescent probe.

RESULTSCompared with BSA-treated cells, the cells treated with AOPPs showed decreased expression of epithelial cell marker E-cadherin and overexpression of mesenchymal marker vimentin and endoplasmic reticulum stress marker GRP78 with an increased ROS level. These changes induced by AOPPs were partly inhibited by arctiin.

CONCLUSIONArctiin can ameliorate AOPP-induced EMT in tubular cells by inhibiting endoplasmic reticulum stress, and oxidative stress response may participate in this process.

Advanced Oxidation Protein Products ; adverse effects ; Cadherins ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; Epithelial Cells ; cytology ; drug effects ; Epithelial-Mesenchymal Transition ; Furans ; pharmacology ; Glucosides ; pharmacology ; Heat-Shock Proteins ; metabolism ; Humans ; Kidney Tubules ; cytology ; drug effects ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Vimentin ; metabolism

OBJECTIVETo investigate whether the p38 mitogen-activated protein kinase (MAPK) signaling pathway mediates advanced oxidation protein products (AOPPs)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells.

METHODSHuman proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA) were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using Western blotting. Western blotting and quantitative RT-PCR were used to examine the protein and mRNA expressions of EMT markers E-cadherin and vimentin and endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to AOPP exposure. The cells treated with AOPPs following pretreatment with salubrinal (an inhibitor of endoplasmic reticulum stress) were also examined for expressions of p38 MAPK and phosphorylated p38 MAPK.

RESULTSAOPP treatment induced the phosphorylation of p38 MAPK in HK-2 cells. AOPP-induced decrease in E-cadherin expression and overexpression of vimentin and GRP78 were partly inhibited by pretreatment of the cells with SB203580. Salubrina partly suppressed AOPP-induced phosphorylation of p38 MAPK in the cells.

CONCLUSIONp38 MAPK signaling pathway, which is regulated by endoplasmic reticulum stress, might mediate AOPP-induced EMT in HK-2 cells.

To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (SV) on proliferation, apoptosis and the PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1. SHI-1 cells were incubated with different concentrations of SV (5, 10, 15 µmol/L). Otherwise, SHI-1 cells without any treatment were used as control. Cells in different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to assay the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis ratio. The human PI3K-AKT Signaling Pathway RT(2) Profiler(TM) PCR Array was used to detect the expression of 84 genes involved in PI3K-AKT signaling. The results indicated that the SV inhibited the proliferation and inducted the apoptosis of SHI-1 cells in time- and dose-dependent manners significantly. The growth inhibition rates of SHI-1 cells treated with 15 µmol/L SV for 24, 48 and 72 h were 26.82, 47.09 and 63.92, respectively; and their early stage apoptosis ratios were 5.75, 13.25 and 15.59, respectively. Compared with the control group, expression levels of 39 genes were changed in the group of 15 µmol/L SV at 48 h, among them 26 genes were down-regulated and 13 genes were up-regulated. It is concluded that the SV can inhibit proliferation and induce apoptosis of SHI-1 cells, and the mechanism may be associated with the changes of gene expression level in PI3K-AKT signaling pathway regulated by SV.
Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Down-Regulation ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Monocytic, Acute ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects ; Simvastatin ; pharmacology

OBJECTIVETo investigate the effect of adiponectin on hepatocyte steatosis.

METHODSL02 cells were transfected with pEGFP-N1-AdipoQ, a plasmid encoding pEGFP-adiponectin fusion protein, or pEGFP-N1. Lipid droplets in the hepatocytes were observed by oil red staining at 72 h. The contents of TG, FFA and glycerol in hepatocytes were measured.

RESULTSCompared to cells transfected with pEGFP-N1-AdipoQ plasmid, much more lipid droplets were observed in cells transfected with pEGFP-N1 plasmid. TG, FFA and glycerol contents in L02 cells and L02/pEGFP-N1 cells were significantly higher than those in L02/pEGFP-N1-AdipoQ cells.

CONCLUSIONSOverexpression of adiponectin prevent hepatocyte steatosis.

Adiponectin ; genetics ; Cell Line ; Fatty Acids, Nonesterified ; analysis ; Fatty Liver ; metabolism ; Genetic Vectors ; Glycerol ; analysis ; Hepatocytes ; cytology ; metabolism ; Humans ; Plasmids ; Recombinant Fusion Proteins ; genetics ; Transfection ; Triglycerides ; analysis

Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Microbubbles ; Oligoribonucleotides, Antisense ; genetics ; Transfection ; methods ; Ultrasonics

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes, including aberrant promoter methylation and histone modification, plays a critical role in human breast carcinogenesis. Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression, thus directly contributing to breast tumorigenesis. Usually, aberrant promoter methylation of TSGs, which can be reversed by pharmacological reagents, occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer. In this review, we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; diagnosis ; drug therapy ; genetics ; metabolism ; CpG Islands ; genetics ; DNA (Cytosine-5-)-Methyltransferases ; antagonists & inhibitors ; therapeutic use ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Silencing ; Humans ; Promoter Regions, Genetic ; Tumor Suppressor Proteins ; genetics ; metabolism