Anisomycin sensitizes non-small-cell lung cancer cells to chemotherapeutic agents and epidermal growth factor receptor inhibitor via suppressing PI3K/Akt/mTOR.

Abstract:

:The poor outcomes in advanced non-small-cell lung cancer (NSCLC) necessitate new treatments. Recent studies emphasize anisomycin as a promising anti-cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard-of-care drugs in NSCLC. We showed that anisomycin inhibited growth, migration, and survival in NSCLC cells regardless of genetic mutation status, and to a greater extent than in normal lung epithelial cells. Isobologram analysis showed that the combination of anisomycin with cisplatin, paclitaxel, or gefitinib was synergistic in NSCLC but not normal lung cells. We further demonstrated that anisomycin inhibited NSCLC growth in mice. The combination of anisomycin with cisplatin was more effective than cisplatin alone and completely arrested NSCLC growth throughout the whole duration of treatment. JNK and p38 MAPK were not required for anisomycin's action. In contrast, anisomycin inhibits PI3K/Akt/mTOR pathway. Overexpression of constitutively active Akt reversed the pro-apoptotic effect of anisomycin. Our work demonstrates the selective anti-NSCLC activity of anisomycin via suppressing PI3K/Akt/mTOR. Our findings provide preclinical evidence to initialize the clinical trial of using anisomycin to sensitize NSCLC to current therapy.

journal_name

Fundam Clin Pharmacol

authors

Tan H,Hu B,Xie F,Zhu C,Cheng Z

doi

10.1111/fcp.12641

subject

Has Abstract

pub_date

2020-12-18 00:00:00

eissn

0767-3981

issn

1472-8206

pub_type

杂志文章
  • Study of in vitro glucuronidation of hydroxyquinolines with bovine liver microsomes.

    abstract::Glucuronidation of drugs by UDP-glucuronosyltransferase (UGT) is a major phase II conjugation reaction. Defects in UGT are associated with Crigler-Najjar syndrome and Gilbert's syndrome with severe hyperbilirubinaemias and jaundice. We analysed the reactivities of some hydroxyquinoline derivatives, which are naturally...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1472-8206.2002.00097.x

    authors: Kanou M,Saeki K,Kato TA,Takahashi K,Mizutani T

    更新日期:2002-12-01 00:00:00

  • Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress.

    abstract::Adverse reactions to antipsychotic drugs (APs) have been attributed to oxidative stress. Sulforaphane (SF) is a potent antioxidant that protects against dopaminergic cell death. We examined the protective properties of SF against AP-induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK-N...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.2011.00988.x

    authors: Mas S,Gassó P,Trias G,Bernardo M,Lafuente A

    更新日期:2012-12-01 00:00:00

  • Effects of tilting in the anaesthetized and mechanically ventilated rat: a model of orthostatic hypotension.

    abstract::The main of the present study was to determine the experimental conditions for an animal model of orthostatic hypotension based on tilting in rats. Blood pressure, heart rate and plasma catecholamine levels were measured before and after tilting in conscious and anaesthetized rats either breathing spontaneously or mec...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1992.tb00092.x

    authors: Pourrias B,Marie C

    更新日期:1992-01-01 00:00:00

  • Relaxation of rabbit middle cerebral arteries in vitro by H1 histaminergic agonists is inhibited by indomethacin and tranylcypromine.

    abstract::The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were ...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1988.tb00648.x

    authors: Ea Kim L,Sercombe R,Oudart N

    更新日期:1988-01-01 00:00:00

  • Do prescribers know the results of key clinical trials? GEP (Groupe d'étude de la Prescription).

    abstract::A survey was run on a sample of 134 French GPs from the Rhône-Alpes region, in an attempt to investigate the way they recollect important clinical trials that should have an impact on their practice. It was found that 1) most of them did not remember these trials (however, the awareness score did vary throughout the t...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1991.tb00721.x

    authors: Reveilleau S,Boissel JP,Alamercery Y

    更新日期:1991-01-01 00:00:00

  • Valsartan and coronary haemodynamics in early post-myocardial infarction in rats.

    abstract::Angiotensin II AT1 receptor blockade (AT1-) has been shown to prolong survival in post-myocardial infarction (MI) heart failure in rats. In this study, we investigated whether an early AT1-induced improvement in coronary vasodilatation reserve (CVR) might be involved in this beneficial effect. Wistar rats with MI were...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1999.tb00374.x

    authors: Gervais M,Richer C,Fornes P,De Gasparo M,Giudicelli JF

    更新日期:1999-01-01 00:00:00

  • Role of bradykinin and tachykinins in the potentiation by enalapril of coughing induced by citric acid in pigs.

    abstract::Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic cough and airway hyperresponsiveness. The aim of this work was to assess in pigs the effects of bradykinin and tac...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1472-8206.2001.00008.x

    authors: Moreaux B,Advenier C,Gustin P

    更新日期:2001-02-01 00:00:00

  • Effect of ellagic acid on cyclosporine A-induced oxidative damage in the liver of rats.

    abstract::Cyclosporine A (CsA) is an immunosuppressor, which is most frequently used in the transplant surgery and in the treatment of autoimmune diseases. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA nephrotoxicity, hepatotoxicity and card...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.2008.00609.x

    authors: Pari L,Sivasankari R

    更新日期:2008-08-01 00:00:00

  • Nitric oxide and the control of renin secretion.

    abstract::Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, renal, immune and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, pituita...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1472-8206.1995.tb00505.x

    authors: Reid IA,Chiu YJ

    更新日期:1995-01-01 00:00:00

  • Quercetin depletes intracellular Ca2+ stores and blunts ATP-triggered Ca2+ signaling in bEnd.3 endothelial cells.

    abstract::Quercetin is a flavonol polyphenol widely found in many vegetables, grains, and fruits. Quercetin has been shown to inhibit proliferation and invasion of various glioma cells and is regarded as a potential anticancer agent against glioma. However, whether and how this drug could affect brain blood vessels and endothel...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12514

    authors: Chen CY,Hour MJ,Shiao LR,Wong KL,Leung YM,Chan P,So EC

    更新日期:2020-04-01 00:00:00

  • Influence of landiolol on the dose requirement of propofol for induction of anesthesia.

    abstract::It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short-acting beta-1-adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control ...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1472-8206.2005.00351.x

    authors: Takizawa D,Saito S,Sato E,Hiraoka H,Kunimoto F,Goto F

    更新日期:2005-10-01 00:00:00

  • Edaravone inhibits procaspase-3 denitrosylation and activation through FasL-Trx2 pathway in KA-induced seizure.

    abstract::Previous studies have demonstrated that excessive free radicals play an essential role in the initiation and progression of epilepsy and that a novel exogenous free radical scavenger edaravone (Ed) exerts some neuroprotective effects on seizure-induced neuronal damage. The purpose of this study was to elucidate the po...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12556

    authors: Hao L,Dong L,Yu Q,Shen W,Wei X

    更新日期:2020-12-01 00:00:00

  • Plasma antioxidative activity during atorvastatin and fluvastatin therapy used in coronary heart disease primary prevention.

    abstract::We estimated the effect of atorvastatin and fluvastatin on plasma antioxidative activity used in coronary heart disease (CHD) primary prevention. Anti-oxidative activity of blood plasma was determined by Bartosz et al. method [Curr. Top. Biophys. (1998)22:11-13], based on reduction of preformed cation radical of 2,2,a...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1046/j.0767-3981.2003.00208.x

    authors: Kowalski J,Pawlicki L,Grycewicz J,Błaszczyk J,Irzmański R,Cegliński T,Kowalczyk E

    更新日期:2004-02-01 00:00:00

  • Dopaminergic and non-dopaminergic pharmacological hypotheses for gait disorders in Parkinson's disease.

    abstract::Gait disorders form one component of the axial disorders observed in Parkinson's disease (PD). Indeed, short steps with a forward-leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with th...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1472-8206.2009.00798.x

    authors: Devos D,Defebvre L,Bordet R

    更新日期:2010-08-01 00:00:00

  • Effects of competitive NMDA receptor antagonists on excitatory amino acid-evoked currents in mouse spinal cord neurones.

    abstract::The effects of CGP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoate] and its ethylester CGP 39551 on whole-cell currents evoked by the endogenous excitatory amino acids, L-glutamate and L-aspartate, were studied in cultured mouse spinal cord neurones. Although CGP 37849 was the more potent compound, both antago...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1999.tb00322.x

    authors: D'Hooge R,Raes A,Van de Vijver G,Van Bogaert PP,De Deyn PP

    更新日期:1999-01-01 00:00:00

  • A GppNHp-insensitivity factor modulates the activation of beta-adrenoceptor-coupled Gs protein in rat cortex and cerebellum.

    abstract::The effect known as the GTP-shift refers to the complete conversion of receptors from the high- to the low agonist-affinity state in the presence of an excess of GTP or one of its analogs. 5'-Guanylylimidodiphosphate (GppNHp) was able to fully suppress the high (-)-isoproterenol-affinity of beta-adrenoceptors (beta AR...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1999.tb00335.x

    authors: Garnier V,Zini R,Tillement JP

    更新日期:1999-01-01 00:00:00

  • Pharmacology and mechanisms of action of new oral anticoagulants.

    abstract::The new oral anticoagulants are announced as an important therapeutic revolution, particularly after their approval by authorities for stroke prevention in atrial fibrillation. However, the pharmacology of these new drugs is not homogeneous. In this review, we summarize the main pharmacological characteristics of the ...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/fcp.12091

    authors: Salem JE,Sabouret P,Funck-Brentano C,Hulot JS

    更新日期:2015-02-01 00:00:00

  • Differential sensitivities of pyrogenic chemokine fevers to CC chemokine receptor 5 antibodies.

    abstract::Macrophage inflammatory protein (MIP)-1beta and RANTES (regulated on activation, normal T-cells expressed and secreted) are members of the CC-family of chemokines. Although these two peptides are structurally and functionally related to one another, each exhibits distinct features, which allows it to independently reg...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.2003.00227.x

    authors: Tavares E,Miñano FJ

    更新日期:2004-04-01 00:00:00

  • Spontaneous adverse event notifications by patients subsequent to the marketing of a new formulation of Levothyrox® amidst a drug media crisis: atypical profile as compared with other drugs.

    abstract::Since patients may report spontaneously adverse events associated with their medications, such notifications are constantly on the rise. In 2017, an unexpected rise of notifications associated with the marketing of a new formula of Levothyrox, differing from the 30-year-old drug only by minor elements, occurred in Fra...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12446

    authors: Viard D,Parassol-Girard N,Romani S,Van Obberghen E,Rocher F,Berriri S,Drici MD

    更新日期:2019-08-01 00:00:00

  • Enhancement on reactive oxygen species and COX-1 mRNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta.

    abstract::This study aimed to investigate the modulation of nitric oxide/reactive oxygen species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside induced relaxation in endothelium-intact (e+) and endothelium-denuded (e-) aortas with greater potency in e+ than in e-. The nitric oxide synthase inhibitor did ...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12103

    authors: Kangussu LM,Olivon VC,Arifa RD,Araújo N,Reis D,Assis MT,Soriani FM,de Souza Dda G,Bendhack LM,Bonaventura D

    更新日期:2015-04-01 00:00:00

  • Restoration of brain protein synthesis in mature and aged rats by a DA agonist, piribedil.

    abstract::Brain ageing affects numerous cerebral metabolic pathways such as cerebral glucose consumption or protein synthesis rate. The pharmacological effect of a mixed D1-D2 dopaminergic agonist, piribedil, on this last metabolism is reported. Cerebral Protein Synthesis Rate (CPSR) was measured by the [35S]L-methionine autora...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1995.tb00521.x

    authors: Bustany P,Trenque T,Crambes O,Moulin M

    更新日期:1995-01-01 00:00:00

  • Can therapeutic efficacy be predicted from phase I data?

    abstract::The aim of phase I studies per se is to explore the tolerance of new compounds which have demonstrated a certain level of activity in animals at sufficiently low non-toxic doses. In most cases, these studies are conducted in 2 steps in a limited number of healthy male volunteers: a single rising dose study followed by...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1472-8206.1990.tb00064.x

    authors: Thiercelin JF

    更新日期:1990-01-01 00:00:00

  • Rabbit articular chondrocytes: an in vitro model for studying the effect of sodium aurothiopropanol sulfonate on proliferation kinetics, type II collagen phenotype and mitochondrial activity.

    abstract::Despite the benefits of chrysotherapy the responsible mechanism of action of gold compounds remains unclear. At a concentration of 5 x 10(-4) M, sodium aurothiopropanol sulfonate (SAS) modified the in vitro proliferation kinetics of articular chondrocytes by reducing growth, viability and plating efficiency. Flow cyto...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1988.tb00621.x

    authors: Ronot X,Hainque B,Christen MO,Froger B,Hartmann DJ,Adolphe M,Lechat P

    更新日期:1988-01-01 00:00:00

  • Pentoxifylline decreases neutrophil respiratory bursts in patients with stable angina.

    abstract::We estimated the effect of pentoxifylline (PTX) on the respiratory burst (examined by chemiluminescence method) of unprimed and primed neutrophils with tumor necrosis factor-alpha (TNF-alpha) in patients with stable angina pectoris. Chemiluminescence of non-stimulated as well as formyl-methionyl-leucyl-phenylalanine (...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1472-8206.1999.tb00345.x

    authors: Kowalski J,Kosmider M,Pasnik J,Zeman K,Baj Z,Janiszewska-Drobinska B,Czekalska R

    更新日期:1999-01-01 00:00:00

  • Mechanism of action of doxepin in the treatment of chronic urticaria.

    abstract::The present study examined 15 patients previously resistant to conventional antihistamines, in which doxepin at doses in the range of 50-75 mg/day was shown to be effective in treatment of chronic urticaria and without significant adverse side effects. However, some controversy remains about its mechanism of action in...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1990.tb00482.x

    authors: Figueiredo A,Ribeiro CA,Gonçalo M,Almeida L,Poiares-Baptista A,Teixeira F

    更新日期:1990-01-01 00:00:00

  • Effect of antimicrobial peptides HNP-1 and hBD-1 on Staphylococcus aureus strains in vitro and in vivo.

    abstract::The aims of this study were: (i) To investigate the activity of recombinant AMPs HNP-1 and hBD-1 in combination with cefotaxime against Staphylococcus aureus strains (MSSA and MRSA) in vitro using checkerboard method; (ii) To investigate the activity of HNP-1 and hBD-1 encapsulated in silicon nanoparticles (niosomes) ...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12499

    authors: Bolatchiev A,Baturin V,Bazikov I,Maltsev A,Kunitsina E

    更新日期:2020-02-01 00:00:00

  • Dopamine formation, from its immediate precursor 3,4-dihydroxyphenylalanine, along the rat digestive tract.

    abstract::The formation of dopamine, from L-3,4-dihydroxyphenylalanine (L-dopa), in fragments of non-glandular and glandular stomach, duodenum, jejunum, ileum and proximal and distal colon of the rat was examined. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (dopac) was also studied. The synthesi...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.1993.tb00237.x

    authors: Vieira-Coelho MA,Soares-da-Silva P

    更新日期:1993-01-01 00:00:00

  • Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

    abstract::Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbitu...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1472-8206.2009.00788.x

    authors: Melo FH,Venâncio ET,de Sousa DP,de França Fonteles MM,de Vasconcelos SM,Viana GS,de Sousa FC

    更新日期:2010-08-01 00:00:00

  • Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

    abstract::To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12463

    authors: Bakhriansyah M,Meyboom RHB,Souverein PC,de Boer A,Klungel OH

    更新日期:2019-10-01 00:00:00

  • Ivabradine improves survival and attenuates cardiac remodeling in isoproterenol-induced myocardial injury.

    abstract::This study investigated whether ivabradine, a selective If current inhibitor reducing heart rate (HR), is able to improve survival and prevent left ventricular (LV) remodeling in isoproterenol-induced heart damage. Wistar rats were treated for 6 weeks: controls (n = 10), ivabradine (10 mg/kg/day orally; n = 10), isopr...

    journal_title:Fundamental & clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/fcp.12620

    authors: Simko F,Baka T,Repova K,Aziriova S,Krajcirovicova K,Paulis L,Adamcova M

    更新日期:2020-10-24 00:00:00