Acta Pharmacologica Sinica (ACTA PHARMACOL SIN)

Publisher: Zhongguo yao li xue hui; Shanghai yao wu yan jiu suo; Zhongguo ke xue yuan, Nature Publishing Group

Journal description

Acta Pharmacologica Sinica, published monthly, is the official journal of the Chinese Pharmacological Society and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. APS was registered as an English international journal in 2000. APS has gained a well-earned reputation during the last two decades for its persisting in reporting researches of high scientific quality.The APS welcomes current original researches on all aspects of life sciences, both experimental and clinical, from any part of the world. Reviews based primarily on authors' own research of internationally important topics are especially welcome.

Current impact factor: 2.50

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.496
2012 Impact Factor 2.354
2011 Impact Factor 1.953
2010 Impact Factor 1.909
2009 Impact Factor 1.783
2008 Impact Factor 1.676
2007 Impact Factor 1.677
2006 Impact Factor 1.397
2005 Impact Factor 1.123
2004 Impact Factor 1.125
2003 Impact Factor 0.884
2002 Impact Factor 0.688
2001 Impact Factor 0.631
1996 Impact Factor 0.197

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.52
Cited half-life 6.20
Immediacy index 0.60
Eigenfactor 0.01
Article influence 0.60
Website Acta Pharmacologica Sinica website
Other titles Acta pharmacologica Sinica (Online), APS, Acta pharmacologica Sinica, Zhongguo yao li xue bao
ISSN 1671-4083
OCLC 51169124
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Nature Publishing Group

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    • Author can archive a pre-print version
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    • 6 months embargo
  • Conditions
    • Authors retain copyright
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    • Publisher's version/PDF cannot be used
    • On author's personal website and institutional repository
    • If funding agency rules apply, authors may post authors version to their relevant funding body's archive, 6 months after publication
    • This policy is an exception to the default policies of 'Nature Publishing Group'
  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is an evolutionarily conserved and lysosome-dependent process for degrading and recycling cellular constituents. Autophagy is activated following an ischemic insult or preconditioning, but it may exert dual roles in cell death or survival during these two processes. Preconditioning or lethal ischemia may trigger autophagy via multiple signaling pathways involving endoplasmic reticulum (ER) stress, AMPK/TSC/mTOR, Beclin 1/BNIP3/SPK2, and FoxO/NF-κB transcription factors, etc. Autophagy then interacts with apoptotic and necrotic signaling pathways to regulate cell death. Autophagy may also maintain cell function by removing protein aggregates or damaged mitochondria. To date, the dual roles of autophagy in ischemia and preconditioning have not been fully clarified. The purpose of the present review is to summarize the recent progress in the mechanisms underlying autophagy activation during ischemia and preconditioning. A better understanding of the dual effects of autophagy in ischemia and preconditioning could help to develop new strategies for the preventive treatment of ischemia.
    Acta Pharmacologica Sinica 03/2015; 36(4). DOI:10.1038/aps.2014.151
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    ABSTRACT: Aim: Interferon-γ inducible protein 16 (IFI16), a DNA sensor for DNA double-strand break (DSB), is expressed in most human hepatocellular carcinoma cell (HCC) lines. In this study we investigated the re-localization of chromatin-bound IFI16 by Nutlin-3, a DNA damage agent, in HCC cells in vitro, and the potential mechanisms. Methods: Human HCC SMMC-7721 (wild-type TP53), Huh-7 (mutant TP53), Hep3B (null TP53) and normal fetal liver L02 cell lines were examined. DSB damage in HCC cells was detected via γH2AX expression and foci formation assay. The expression of IFI16 and IFNB mRNA was measured using RT-PCR, and subcellular localization and expression of the IFI16 protein were detected using chromatin fractionation, Western blot analysis, and fluorescence microscopy. Results: Treatment of SMMC-7721 cells with Nutlin-3 (10 μmol/L) or etoposide (40 μmol/L) induced significant DSB damage. In SMMC-7721 cells, Nutlin-3 significantly increased the expression levels of IFI16 and IFNB mRNA, and partially redistributed chromatin-bound IFI16 protein to the cytoplasm. These effects were blocked by pretreatment with pifithrin-α, a p53 inhibitor. Furthermore, Nutlin-3 did not induce ectopic expression of IFI16 protein in Huh-7 and Hep3B cells. Moreover, the association of IFI16 with chromatin and Nutlin-3-induced changes in localization were not detected in L02 cells. Conclusion: Nutlin-3 regulates the subcellular localization of IFI16 in HCC cells in vitro in a p53-dependent manner.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.106
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    ABSTRACT: Aim: To study the effects of tanshinone IIA (TIIA) on lipopolysaccharide (LPS)-induced acute lung injury in mice and the underlying mechanisms. Methods: Mice were injected with LPS (10 mg/kg, ip), then treated with TIIA (10 mg/kg, ip). Seven hours after LPS injection, the lungs were collected for histological study. Protein, LDH, TNF-α and IL-1β levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in lungs were measured. Cell apoptosis and Bcl-2, caspase-3, NF-κB and HIF-1α expression in lungs were assayed. Results: LPS caused marked histological changes in lungs, accompanied by significantly increased lung W/D ratio, protein content and LDH level in BALF, and Evans blue leakage. LPS markedly increased neutrophil infiltration in lungs and inflammatory cytokines in BALF. Furthermore, LPS induced cell apoptosis in lungs, as evidenced by increased TUNEL-positive cells, decreased Bcl-2 content and increased cleaved caspase-3 content. Moreover, LPS significantly increased the expression of NF-κB and HIF-1α in lungs. Treatment of LPS-injected mice with TIIA significantly alleviated these pathological changes in lungs. Conclusion: TIIA alleviates LPS-induced acute lung injury in mice by suppressing inflammatory responses and apoptosis, which is mediated via inhibition of the NF-κB and HIF-1α pathways.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.112
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    ABSTRACT: Aim:Small GTPase Rac1 is a member of the Ras superfamily, which plays important roles in regulation of cytoskeleton reorganization, cell growth, proliferation, migration, etc. The aim of this study was to determine how a constitutively active Rac1b regulated cell proliferation and to investigate the effects of the Rac1b inhibitor sanguinarine.Methods:Three HEK293T cell lines stably overexpressing GFP, Rac1-GFP or Rac1b-GFP were constructed by lentiviral infection. The cells were treated with sanguinarine (1 μmol/L) or its analogue berberine (1 μmol/L) for 4 d. Cell proliferation was evaluated by counting cell numbers and with a BrdU incorporation assay. The levels of cleaved PARP-89 (an apoptosis marker) and cyclin-D1 (a proliferative index) were measured using Western blotting.Results:In 10% serum-containing media, overexpressing either Rac1 or Rac1b did not significantly change the cell proliferation. In the serum-starved media, however, the survival rate of Rac1b cells was significantly increased, whereas that of Rac1 cells was moderately increased. The level of cleaved PARP-89 was significantly increased in serum-starved Rac1 cells, but markedly reduced in serum-starved Rac1b cells. The level of cyclin-D1 was significantly increased in both serum-starved Rac1 and Rac1b cells. Treatment with sanguinarine, but not berberine, inhibited the proliferation of Rac1b cells, which was accompanied by significantly increased the level of PARP-89, and decreased both the level of cyclin-D1 and the percentage of BrdU positive cells.Conclusion:Rac1b enhances the cell proliferation under a growth-limiting condition via both anti-apoptotic and pro-proliferative mechanisms. Sanguinarine, as the specific inhibitor of Rac1b, is a potential therapeutic agent for malignant tumors with up-regulated Rac1b.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.115
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    ABSTRACT: Neurotrophins are involved in many physiological and pathological processes in the nervous system. They regulate and modify signal transduction, transcription and translation in neurons. It is recently demonstrated that the neurotrophin expression is regulated by microRNAs (miRNAs), changing our views on neurotrophins and miRNAs. Generally, miRNAs regulate neurotrophins and their receptors in at least two ways: (1) miRNAs bind directly to the 3' untranslated region (UTR) of isoform-specific mRNAs and post-transcriptionally regulate their expression; (2) miRNAs bind to the 3' UTR of the regulatory factors of neurotrophins and regulate their expression. On the other hand, neurotrophins can regulate miRNAs. The results of BNDF research show that neurotrophins regulate miRNAs in at least three ways: (1) ERK stimulation enhances the activation of TRBP (HIV-1 TAR RNA-binding protein) and Dicer, leading to the upregulation of miRNA biogenesis; (2) ERK-dependent upregulation of Lin28a (RNA-binding proteins) blocks select miRNA biogenesis; (3) transcriptional regulation of miRNA expression through activation of transcription factors, including CREB and NF-κB. These regulatory processes integrate positive and negative regulatory loops in neurotrophin and miRNA signaling pathways, and also expand the function of neurotrophins and miRNAs. In this review, we summarize the current knowledge of the regulatory networks between neurotrophins and miRNAs in brain diseases and cancers, for which novel cutting edge therapeutic, delivery and diagnostic approaches are emerging.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.135
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    ABSTRACT: Aim: To investigate the therapeutic effects of resveratrol (RSV) on periodontitis in diabetic mice and to explore the underlying mechanisms in vitro. Methods: Experimental periodontitis was induced in db/db mice by ligature application of porphyromonas gingivalis. The mice were treated with RSV (20 mg/kg, po) daily for 4 weeks. Alveolar bone loss, proinflammatory cytokines and TLR4 expression in the gingival tissue were measured. Cultured gingival epithelial cells (GECs) were used for in vitro studies. The transcriptional activity of TLR4 downstream signaling was analyzed using Western blotting. Results: RSV administration significantly decreased the blood glucose levels, and ameliorated alveolar bone loss in db/db mice with experimental periodontitis. RSV administration also suppressed the high levels of IL-1β, IL-6, IL-8, TNF-α, and TLR4 in gingival tissue of the mice. In the GECs incubated in high glucose medium, TLR4 expression was substantially upregulated, which was partly blocked in the presence of RSV. Lipopolysaccharides markedly increased the expression and secretion of IL-1β, IL-6, IL-8, and TNF-α in the GECs cultured in high glucose medium, which was also partly blocked in the presence of RSV. Furthermore, RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3. Conclusion: RSV exerts protective effects against experimental periodontitis in db/db mice via negative regulation of TLR4 signaling.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.131
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.116
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    ABSTRACT: Nuclear receptors (NRs) are members of a large superfamily of evolutionarily related transcription factors that control a plethora of biological processes. NRs orchestrate complex events such as development, organ homeostasis, metabolism, immune function, and reproduction. Approximately one-half of the 48 human NRs have been shown to act as ligand-regulated transcription factors and respond directly to a large variety of endogenous hormones and metabolites that are generally hydrophobic and small in size (eg, retinoic acid or estradiol). The second half of the NR family comprises the so-called orphan receptors, for which regulatory ligands are still unknown or may not exist despite the presence of a C-terminal ligand-binding domain, which is the hallmark of all NRs. Several chemicals released into the environment (eg, bisphenols, phthalates, parabens, etc) share some physicochemical properties with natural ligands, allowing them to bind to NRs and activate or inhibit their action. Collectively referred to as endocrine disruptors or endocrine-disrupting chemicals (EDCs), these environmental pollutants are highly suspected to cause a wide range of developmental, reproductive, neurological, or metabolic defects in humans and wildlife. Crystallographic studies are revealing unanticipated mechanisms by which chemically diverse EDCs interact with the ligand-binding domain of NRs. These studies thereby provide a rational basis for designing novel chemicals with lower impacts on human and animal health. In this review, we provide a structural and mechanistic view of endocrine disrupting action using estrogen receptors α and β, (ERα/β), peroxisome proliferator activated receptor γ (PPARγ), and their respective environmental ligands as representative examples.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.133
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    ABSTRACT: The constitutive androstane receptor (CAR) is initially defined as a xenobiotic nuclear receptor that protects the liver from injury. Detoxification of damaging chemicals is achieved by CAR-mediated induction of drug-metabolizing enzymes and transporters. More recent research has implicated CAR in energy metabolism, suggesting a therapeutic potential for CAR in metabolic diseases, such as type 2 diabetes and obesity. A better understanding of the mechanisms by which CAR regulates energy metabolism will allow us to take advantage of its effectiveness while avoiding its side effects. This review summarizes the current progress on the regulation of CAR nuclear translocation, upstream modulators of CAR activity, and the crosstalk between CAR and other transcriptional factors, with the aim of elucidating how CAR regulates glucose and lipid metabolism.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.102
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    ABSTRACT: Nuclear receptors (NRs) are ligand-regulated transcription factors that regulate metabolism, development and immunity. The NR superfamily is one of the major classes of drug targets for human diseases. Retinoic acid receptor-related orphan receptor (ROR) α, β and γ belong to the NR superfamily, and these receptors are still considered as 'orphan' receptors because the identification of their endogenous ligands has been controversial. Recent studies have demonstrated that these receptors are regulated by synthetic ligands, thus emerge as important drug targets for the treatment of multiple sclerosis, rheumatoid arthritis, psoriasis, etc. Studying the structural basis and ligand development of RORs will pave the way for a better understanding of the roles of these receptors in human diseases. Here, we review the structural basis, disease relevance, strategies for ligand identification, and current status of development of therapeutic ligands for RORs.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.120
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    ABSTRACT: Bile acids (BAs) are traditionally considered as "physiological detergents" for emulsifying hydrophobic lipids and vitamins due to their amphipathic nature. But accumulating clinical and experimental evidence shows an association between disrupted BA homeostasis and various liver disease conditions including hepatitis infection, diabetes and cancer. Consequently, BA homeostasis regulation has become a field of heavy interest and investigation. After identification of the Farnesoid X Receptor (FXR) as an endogenous receptor for BAs, several nuclear receptors (SHP, HNF4α, and LRH-1) were also found to be important in regulation of BA homeostasis. Some post-translational modifications of these nuclear receptors have been demonstrated, but their physiological significance is still elusive. Gut secrets FGF15/19 that can activate hepatic FGFR4 and its downstream signaling cascade, leading to repressed hepatic BA biosynthesis. However, the link between the activated kinases and these nuclear receptors is not fully elucidated. Here, we review the recent literature on signal crosstalk in BA homeostasis.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.118
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    ABSTRACT: Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.117
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    ABSTRACT: Aim:Sitagliptin, an oral glucose-lowering agent, has been found to produce cardiovascular protection possibly via anti-inflammatory and anti-atherosclerotic activities of glucagon-like peptide-1 receptor (GLP-1). The aim of this study was to investigate whether sitagliptin protected the kidney function from acute ischemia-reperfusion (IR) injury in rats.Methods:Adult male SD rats were categorized into 4 groups: sham control, IR injury, IR+sitagliptin (300 mg/kg) and IR+sitagliptin (600 mg/kg). Acute renal IR injury of both kidneys was induced by clamping the renal pedicles for 1 h. The drug was orally administered at 1, 24 and 48 h after acute IR. Blood samples and 24-h urine were collected before and at 72 h after acute IR. Then the rats were sacrificed, and the kidneys were harvested for biochemical and immunohistochemical studies.Results:Acute IR procedure markedly increased serum levels of creatinine and BUN and the ratio of urine protein to creatinine. The kidney injury score, inflammatory biomarkers (MMP-9, TNF-α and NF-κB) levels and CD68+ cells in IR kidneys were considerably increased. The expression of oxidized protein, reactive oxygen species (NOX-1, NOX-2) and apoptosis proteins (Bax, caspase-3, PARP) in IR kidneys was also significantly upregulated. All these pathological changes were suppressed by sitagliptin in a dose-dependent manner. Furthermore, the serum GLP-1 level, and the expression of GLP-1 receptor, anti-oxidant biomarkers (HO-1 and NQO-1 cells, as well as SOD-1, NQO-1 and HO-1 proteins), and angiogenesis markers (SDF-1α+ and CXCR4+ cells) in IR kidneys were significantly increased, and further upregulated by sitagliptin.Conclusion:Sitagliptin dose-dependently protects rat kidneys from acute IR injury via upregulation of serum GLP-1 and GLP-1 receptor expression in kidneys.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.98
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    ABSTRACT: Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, ERα and ERβ, function as hormone-dependent transcription factors that directly regulate the expression of their target genes. Therefore, a better understanding of the function and regulation of estrogen-responsive genes provides insight into the gene regulation network associated with breast cancer. Recent technological developments in high-throughput sequencing have enabled the genome-wide identification of estrogen-responsive genes. Further elucidating the estrogen gene cascade is critical for advancements in the diagnosis and treatment of breast cancer.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.123
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    ABSTRACT: Aim: To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication. Methods: A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check. Results: A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (≥65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus. Conclusion: Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus.
    Acta Pharmacologica Sinica 12/2014; 36(2). DOI:10.1038/aps.2014.110
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    ABSTRACT: Aim:To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality.Methods:CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining.Results:CAP/NPs had an average diameter of 82.54±0.51 nm, high drug-loading capacity of 14.0%±0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation.Conclusion:CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.113
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    ABSTRACT: G226 is a novel derivative of epipolythiodioxopiperazines with potent inhibitory activity against cancer cells. Here, we sought to identify potential targets involved in the anti-cancer activity of G226. Cell proliferation assay was conducted in a panel of 12 human cancer cell lines. The activities of topoisomerase I (Topo I) and Topo II were studied using supercoiled pBR322 DNA relaxation and kDNA decatenation assays. ROS production was assessed with probes DCFH-DA and H&E. Western blot analysis and flow cytometry were used to examine DNA damage, apoptosis and cell cycle changes. G226 displayed potent cytotoxicity in the 12 human cancer cell lines with a mean IC50 value of 92.7 nmol/L. This compound (1-100 μmol/L) selectively inhibited the activity of Topo II, and elevated the expression of phosphorylated-H2AX in a dose-dependent manner. In Topo II-deficient HL60/MX2 cells, however, G226-induced DNA damage, apoptosis and cytotoxicity were only partially reduced, suggesting that Topo II was not essential for the anti-tumor effects of G226. Furthermore, G226 (0.125-2 μmol/L) dose-dependently elevated the intracellular levels of H2O2 and in the cancer cells, and pretreatment with GSH, NAC or DTT not only blocked G226-induced intracellular accumulation of ROS, but also abrogated G226-mediated phosphorylation of H2AX, apoptosis and cytotoxicity. G226-mediated ROS production contributes to the anti-cancer activity of this compound.
    Acta Pharmacologica Sinica 12/2014; 35(12):1546-55. DOI:10.1038/aps.2014.105
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    ABSTRACT: Aim:β, β-Dimethylacrylshikonin (DMAS) is an anticancer compound extracted from the roots of Lithospermum erythrorhizon. In the present study, we investigated the effects of DMAS on human lung adenocarcinoma cells in vitro and explored the mechanisms of its anti-cancer action.Methods:Human lung adenocarcinoma A549 cells were tested. Cell viability was assessed using an MTT assay, and cell apoptosis was evaluated with flow cytometry and DAPI staining. The expression of the related proteins was detected using Western blotting. The mitochondrial membrane potential was measured using a JC-1 kit, and subcellular distribution of cytochrome c was analyzed using immunofluorescence staining.Results:Treatment of A549 cells with DMAS suppressed the cell viability in dose- and time-dependent manners (the IC50 value was 14.22 and 10.61 μmol/L, respectively, at 24 and 48 h). DMAS (7.5, 10, and 15 μmol/L) dose-dependently induced apoptosis, down-regulated cIAP-2 and XIAP expression, and up-regulated Bax and Bak expression in the cells. Furthermore, DMAS resulted in loss of mitochondrial membrane potential and release of cytochrome c in the cells, and activated caspase-9, caspase-8, and caspase-3, and subsequently cleaved PARP, which was abolished by pretreatment with Z-VAD-FMK, a pan-caspase inhibitor. DMAS induced sustained p38 phosphorylation in the cells, while pretreatment with SB203580, a specific p38 inhibitor, blocked DMAS-induced p38 activation and apoptosis.Conclusion:DMAS inhibits the growth of human lung adenocarcinoma A549 cells in vitro via activation of p38 signaling pathway.
    Acta Pharmacologica Sinica 12/2014; 36(1). DOI:10.1038/aps.2014.108