Abstract:
:Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure-activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2'-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 μM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive valepotriate derivatives.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Yan YY,Shi KY,Teng F,Chen J,Che JX,Dong XW,Lin NM,Zhang Bdoi
10.1038/s41401-019-0354-1subject
Has Abstractpub_date
2020-06-01 00:00:00pages
835-842issue
6eissn
1671-4083issn
1745-7254pii
10.1038/s41401-019-0354-1journal_volume
41pub_type
杂志文章abstract:AIM:To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor kappaB (NF-kappaB) signal as the target. METHODS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00536.x
更新日期:2007-03-01 00:00:00
abstract:AIM:To investigate the role of c-Jun N-terminal protein kinase 1 and 2 (JNK1/2) and the main signal pathway for its activation in hydrogen peroxide (H(2)O(2)) induced apoptotic-like cortical cell death. METHODS:Using the model of oxidative stress induced by H(2)O(2), the expression and diphosphorylation of JNK1/2 was ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract::Cocaine is one of the most abused illicit drugs worldwide. It is well known that the dopamine (DA) transporter is its major target; but cocaine also acts on other targets including nicotinic acetylcholine receptors (nAChRs). In this study, we investigated the effects of cocaine on a special subtype of neuronal nAChR, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0276-y
更新日期:2020-02-01 00:00:00
abstract:AIM:To develop and validate a novel precolumn derivatization method for the quantitative determination and pharmacokinetic application of acetylshikonin in macaque monkeys by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). METHODS:2-Mercaptoethanol was added to the blood sample a...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00898.x
更新日期:2008-12-01 00:00:00
abstract:AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.42
更新日期:2013-07-01 00:00:00
abstract:AIM:To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice. METHODS:An asthmatic mouse model was established and treated with CpG ODN. Total inflammatory cells and eosinophils ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00157.x
更新日期:2005-09-01 00:00:00
abstract:AIM:The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS:Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine (10(-5) mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. T...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-018-0165-9
更新日期:2019-07-01 00:00:00
abstract:AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:AIM:To investigate whether or not brain histamine was involved in memory deficits induced by lesions of nucleus basalis magnocellularis (NBM) in rats. METHODS:Passive avoidance response was used to measure memory process in rats, and NBM was bilaterally lesioned by injection of ibotenic acid (6 microg/site). RESULTS:...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract:AIM:To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro. METHODS:Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Weste...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00550.x
更新日期:2007-07-01 00:00:00
abstract::Type capital I, Ukrainian natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Valphabeta TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type capital...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2010.119
更新日期:2010-09-01 00:00:00
abstract::Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservati...
journal_title:Acta pharmacologica Sinica
pub_type: 历史文章,杂志文章,评审
doi:10.1038/aps.2017.182
更新日期:2018-05-01 00:00:00
abstract:AIM:To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS:The experimental model of AS in rats were established by intraperitioneal injection of vit...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00106.x
更新日期:2005-07-01 00:00:00
abstract:AIM:To investigate the ability of an antisense RNA eukaryotic expression plasmid pcDNA3.1/survivin in down-regulating the expression level of survivin mRNA and survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant HL-60/ADR cell line. METHODS:The expression of survivin mRNA was measured by R...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:AIM:High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play pivotal roles in vascular inflammation and atherosclerosis. The aim of this study was to determine whether the HMGB1-RAGE axis was involved in the actions of simvastatin on vascular inflammation and atheroscler...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.8
更新日期:2013-06-01 00:00:00
abstract:AIM:To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine (LPC), the major component of oxidized low-density lipoprotein, in rat thoracic aorta. METHODS:Both the endotheliu...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00013.x
更新日期:2005-01-01 00:00:00
abstract:AIM:To investigate the modulatory effect of CJZ3, a lomerizine derivative, on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC). METHODS:RBMEC were isolated and cultured in Dulbecco modified Eagle medium/F12 (1:1) medium, and the amount of intracellular rhodamine 123 (Rh123) was determi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00294.x
更新日期:2006-04-01 00:00:00
abstract::Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.139
更新日期:2018-04-01 00:00:00
abstract:AIM:The changes of seizure susceptibility of transgenic mice overexpressing GABA transporter-1 (GAT-1) were studied to clarify the possible role of GABAergic transmission in epileptogenesis. METHODS:Seizures were induced by intraperitoneal administration of pentylenetetrazol (PTZ), picrotoxin (PIC), or kainic acid (KA...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosab...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2013.181
更新日期:2014-03-01 00:00:00
abstract:AIM:To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). METHODS:The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newl...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:AIM:Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS:Cell proliferation, DNA fragmentation, Ann...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.15
更新日期:2014-06-01 00:00:00
abstract:AIM:To find novel proteins that may bind to alpha1A-adrenergic receptor (alpha1A-AR) and investigate their interactions with the other two alpha1-AR subtypes (alpha1B-AR and alpha1D-AR) with an expectation to provide new leads for the function study of the receptors. METHODS:Yeast two-hybrid assay was performed to scr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract:AIM:To examine if steroid-like compounds found in many Chinese medicinal products conventionally used for the promotion of blood circulation may act as active components via the same molecular mechanism triggered by cardiac glycosides, such as ouabain. METHODS:The inhibitory potency of ouabain and the identified stero...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.61
更新日期:2010-06-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) have become an essential research platform to study different human diseases once being discovered by Dr. Shinya Yamanaka in 2006. Another breakthrough in biomedical research is the application of CRISPR/Cas9 system for genome editing in mammalian cells. Although numerous studies...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0452-0
更新日期:2020-11-01 00:00:00
abstract::The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on va...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0445-z
更新日期:2020-07-23 00:00:00
abstract:AIM:To study the antioxidant, activity of Qizhu Tang (QZT) both in vivo and in vitro. METHODS:QZT consists of 4 herbal constituents (Rhizoma Atractylodis Macrocephalae, Poria cocos, Kadix Notoginseng, and Radix Astragali), each of the components and their combinations were examined in vitro for 1, 1-diphenyl-2-picrylh...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Recently, two different chemicals have been matched as ligands with the same G-protein-coupled receptor (GPCR). Double-pairing of OGR1 family GPCRs with proton and lysolipid raises several questions. First, whether both are the real ligands for the GPCRs. Second, whether modulation of a GPCR by two chemicals could be ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00237.x
更新日期:2005-12-01 00:00:00
abstract:AIM:To investigate the effects of the cardiotonic steroid, ouabain, on cardiac differentiation of murine embyronic stem cells (mESCs). METHODS:Cardiac differentiation of murine ESCs was enhanced by standard hanging drop method in the presence of ouabain (20 μmol/L) for 7 d. The dissociated ES derived cardiomyocytes we...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.188
更新日期:2011-01-01 00:00:00