Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.


:Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment.


Biochem Pharmacol


Biochemical pharmacology


Ko JC,Zheng HY,Chen WC,Peng YS,Wu CH,Wei CL,Chen JC,Lin YW




Has Abstract


2016-12-15 00:00:00












  • Inhibition of phagocyte chemotaxis by uteroglobin, an inhibitor of blastocyst rejection.

    abstract::Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vasanthakumar G,Manjunath R,Mukherjee AB,Warabi H,Schiffmann E

    更新日期:1988-02-01 00:00:00

  • 2,5-Hexanedione modifies skeletal proteins of the red blood cells and increases the binding of hemoglobin to the membrane.

    abstract::The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mallozzi C,Scorza G,Frontali N,Minetti M

    更新日期:1989-08-15 00:00:00

  • Influence of di- and tri-phenylethylene estrogen/antiestrogen structure on the mechanisms of protein kinase C inhibition and activation as revealed by a multivariate analysis.

    abstract::We have performed a systematic study of the interaction of 36 di- and tri-phenylethylene derivatives (DPEs and TPEs) with protein kinase C (PKC). The results were submitted to a multivariate analysis in order to identify the structural features that might be implicated in interference with the activity of three PKC su...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bignon E,Pons M,Doré JC,Gilbert J,Ojasoo T,Miquel JF,Raynaud JP,Crastes de Paulet A

    更新日期:1991-09-12 00:00:00

  • Unequivocal synthesis and characterisation of dopamine 3- and 4-O-sulphates.

    abstract::The major metabolic products of the endogeneous catecholamine dopamine are its 3- and 4-O-sulphates which have also been implicated as intermediates in noradrenaline biosynthesis. Because of the unsatisfactory status of the literature concerning the synthesis, isolation, purity and characterisation of the dopamine O-s...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Osikowska BA,Idle JR,Swinbourne FJ,Sever PS

    更新日期:1982-07-01 00:00:00

  • Inhibition of mitochondrial fatty acid oxidation in pentenoic acid-induced fatty liver. A possible model for Reye's syndrome.

    abstract::Rats treated with six to eight doses (80 mg/kg, i.p.) of 4-pentenoic acid, an inhibitor of mitochondrial fatty acid oxidation in vitro, during a 48-hr starvation period developed microvesicular fatty infiltration of the liver similar to that observed in Reye's Syndrome. Hepatic triglycerides were elevated an average o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Thayer WS

    更新日期:1984-04-15 00:00:00

  • Effect of 3-aminobenzamide on antigenic variation of Trypanosoma brucei.

    abstract::African trypanosomes, like Trypanosoma brucei, depend on antigenic variation to evade the immune response of the vertebrate host. An antigenic switch corresponds to the activation of a variable surface glycoprotein (VSG) gene from a large silent repertoire. Most switches require the duplicative transposition of a VSG ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cornelissen AW,Michels PA,Borst P,Spanjer W,Versluijs-Broers JA,Van der Meer C,Farzaneh F,Shall S

    更新日期:1985-12-01 00:00:00

  • Antioxidant activity of adrenergic agents derived from catechol.

    abstract::The ability of adrenergic catechol derivatives, including dobutamine, dopamine, and isoproterenol, to inhibit lipid peroxidation was examined. All the catechol derivatives we tested strongly inhibited lipid peroxidation. Dobutamine was a more powerful inhibitor of iron-catalyzed lipid peroxidation than the other agent...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Miura T,Muraoka S,Ogiso T

    更新日期:1998-06-15 00:00:00

  • Disruption of Plasmodium falciparum-infected erythrocyte cytoadherence to human melanoma cells with inhibitors of glycoprotein processing.

    abstract::Adherence of Plasmodium falciparum-infected erythrocytes (IE) to the venular endothelium in brain and other organs is characteristic of cerebral malaria, an often fatal complication in infected individuals. It has been shown that cytoadherence may be mediated through interaction of IE with glycoproteins on host target...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wright PS,Cross-Doersen DE,Schroeder KK,Bowlin TL,McCann PP,Bitonti AJ

    更新日期:1991-06-15 00:00:00

  • Castanospermine-glucosides as selective disaccharidase inhibitors.

    abstract::Castanospermine (CS) is a potent but non-selective inhibitor of many glycohydrolases including the intestinal disaccharidases. Several CS-glucosides were synthesized to investigate the effect of an attached glucopyranosyl residue on the potency and selectivity of CS toward inhibition of intestinal disaccharidases. 8 a...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rhinehart BL,Robinson KM,King CH,Liu PS

    更新日期:1990-05-15 00:00:00

  • Effects of chronic administration of the peroxisome proliferator, clofibrate, on cytosolic acetyl-CoA hydrolase in rat liver.

    abstract::The hypolipidemic drug ethyl chlorophenoxyisobutyrate (clofibrate) is known to induce peroxisome proliferation and to be carcinogenic after long term administration to rats and mice. We examined the effects of treatment with this drug for periods of up to 18 months on cytosolic ATP-stimulated and ADP-inhibited acetyl-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nakanishi Y,Okamoto K,Isohashi F

    更新日期:1993-04-06 00:00:00

  • A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling.

    abstract::Originally discovered as an anti-fungal agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a promising anti-cancer drug. In complex with its cellular receptor, the FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of the mammalian target of rapamycin (mTOR). By mediating...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Chen J,Fang Y

    更新日期:2002-10-01 00:00:00

  • Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo.

    abstract::Multidrug resistance (MDR) is a phenomenon where cancer cells become simultaneously resistant to anticancer drugs with different structures and mechanisms of action. MDR has been shown to be associated with overexpression of ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small molecule tyro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sodani K,Patel A,Anreddy N,Singh S,Yang DH,Kathawala RJ,Kumar P,Talele TT,Chen ZS

    更新日期:2014-05-01 00:00:00

  • Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs.

    abstract::Nucleoside analogs used in antiviral therapies need to be phosphorylated to their tri-phospho counterparts in order to be active on their cellular target. Human phosphoglycerate kinase (hPGK) was recently reported to participate in the last step of phosphorylation of cytidine L-nucleotide derivatives [Krishnan PGE, La...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gallois-Montbrun S,Faraj A,Seclaman E,Sommadossi JP,Deville-Bonne D,Véron M

    更新日期:2004-11-01 00:00:00

  • Activation pathways of 5-fluorouracil in rat organs and in PC12 cells.

    abstract::Activation of the pyrimidine analogue 5-fluorouracil (5-FU) to the ribonucleotide level may occur through one of the following three pathways: 1) the 5-phosphoribosyl 1-pyrophosphate (PRPP)-mediated direct transfer of ribose 5-phosphate to 5-FU as catalysed by orotate phosphoribosyltransferase; 2) the ribose 1-phospha...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mascia L,Ipata PL

    更新日期:2001-07-15 00:00:00

  • On Becoming a Pharmacologist: Channeling David Triggle.

    abstract::This Festschrift contribution summarizes the perspectives of two of David Triggle's graduate students. Both share somewhat parallel scientific and career paths-i.e., enrolling in the Biochemical Pharmacology program at the University of Buffalo, pursuing graduate training under the mentorship of David Triggle and subs...

    journal_title:Biochemical pharmacology

    pub_type: 历史文章,杂志文章,评审


    authors: Rampe D,Gopalakrishnan M

    更新日期:2015-11-15 00:00:00

  • Clavilactones, a novel class of tyrosine kinase inhibitors of fungal origin.

    abstract::Targeting of deregulated protein tyrosine kinases has been proposed as a new approach in the therapeutic intervention against pathological processes including proliferative disorders and cancer. Using a screening approach based on a comparative evaluation of antiproliferative effects in a panel of tumor cells with dif...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cassinelli G,Lanzi C,Pensa T,Gambetta RA,Nasini G,Cuccuru G,Cassinis M,Pratesi G,Polizzi D,Tortoreto M,Zunino F

    更新日期:2000-06-15 00:00:00

  • The effect of diabetes on the in vivo acetylation capacity of the spontaneously diabetic, insulin-dependent BB/Edinburgh Wistar rat.

    abstract::In contrast to previous studies using chemically-induced diabetic rats, the in vivo acetylation of sulphamethazine is increased in spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) Wistar rats compared to non-diabetic control animals from the same colony. In both diabetic and non-diabetic rats, male animal...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lindsay RM,Baird JD

    更新日期:1991-02-01 00:00:00

  • Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies.

    abstract::Primary hepatocyte cultures derived from rat, rabbit, guinea pig and monkey have been treated in vitro with metabolites of di(2-ethylhexyl)phthalate, i.e. mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (metabolite V) and mono(2-ethyl-5-oxohexyl)phthalate (metabolite VI). In rat hepatocyte c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dirven HA,van den Broek PH,Peeters MC,Peters JG,Mennes WC,Blaauboer BJ,Noordhoek J,Jongeneelen FJ

    更新日期:1993-06-22 00:00:00

  • Induction of P4502E1 by acetone in isolated rabbit hepatocytes. Role of increased protein and mRNA synthesis.

    abstract::The molecular mechanism(s) underlying induction of the hepatic microsomal cytochrome P4502E1 (2E1) by xenobiotics (e.g. ethanol and acetone) is controversial. Proposed mechanisms include increased rates of enzyme synthesis due to elevated 2E1 mRNA levels, enhanced translation of pre-existing mRNA, or stabilization of ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kraner JC,Lasker JM,Corcoran GB,Ray SD,Raucy JL

    更新日期:1993-04-06 00:00:00

  • Vasoactive intestinal polypeptide does not affect thyroid follicular cell membrane potential or input resistance.

    abstract::It has been suggested that vasoactive intestinal polypeptide (VIP) has a role as a neurotransmitter and that it participates in the control of hormone release from thyroid follicles. Many hormones and neurotransmitters alter the ionic permeability properties of the plasma membrane of their target cells when they bind ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Green ST

    更新日期:1987-12-15 00:00:00

  • The super-cooling compound icilin stimulates c-Fos and Egr-1 expression and activity involving TRPM8 channel activation, Ca2+ ion influx and activation of the ternary complex factor Elk-1.

    abstract::The TRPM8 cation channel can be activated by the cooling compound icilin. Recently, we showed that stimulation of TRPM8 channels induces a signaling cascade leading to the activation of the transcription factor AP-1. Additionally, expression of the AP-1 constituent c-Fos has been shown to be induced following TRPM8 st...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ulrich M,Wissenbach U,Thiel G

    更新日期:2020-07-01 00:00:00

  • The effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.

    abstract::The effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione lev...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lind MJ,McGown AT,Hadfield JA,Thatcher N,Crowther D,Fox BW

    更新日期:1989-06-01 00:00:00

  • Acute and chronic in vivo therapeutic resistance.

    abstract::The response and engagement of host normal tissues in malignant disease are major factors in therapeutic resistance. Physically, solid tumors have regions of hypoxia and acidosis. These physical stresses can lead to a more aggressive malignant phenotype through activation of HIF, GLUT-1, carbonic anhydrase IX, and sub...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Teicher BA

    更新日期:2009-06-01 00:00:00

  • LPS-induced dissociation of multidrug resistance-associated protein 2 (Mrp2) and radixin is associated with Mrp2 selective internalization in rats.

    abstract::Multidrug resistance-associated protein 2 (Mrp2) is an ATP-dependent export pump that mediates the formation of bile-salt-independent bile flow. Disruption of the canalicular localization of Mrp2, without changes in its expression, is observed in chronic liver failure and is accompanied by oxidative stress. We reporte...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Saeki J,Sekine S,Horie T

    更新日期:2011-01-01 00:00:00

  • Pharmacological modulation of human platelet leukotriene C4-synthase.

    abstract::The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sala A,Folco G,Henson PM,Murphy RC

    更新日期:1997-03-21 00:00:00

  • Neurotoxic esterase: characterization of the solubilized enzyme and the conditions for its solubilization from chicken brain microsomal membranes with ionic, zwitterionic, or nonionic detergents.

    abstract::Neurotoxic esterase (NTE) is a membrane-bound protein found in highest concentration in brain and lymphocytes. The enzyme has no known physiological function, but its organophosphorylation and aging in neural tissue are thought to trigger the pathogenesis of organophosphorus-induced delayed neuropathy (OPIDN). Solubil...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Davis CS,Richardson RJ

    更新日期:1987-05-01 00:00:00

  • Griseofulvin: a novel interaction with bovine brain tubulin.

    abstract::Griseofulvin is an anti-fungal drug whose mechanism of action is directed against microtubules. Although it inhibits the assembly of mammalian brain tubulin, its binding to tubulin has not been directly measured successfully. We have examined the interaction of griseofulvin with tubulin fluorometrically by measuring t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Chaudhuri AR,Ludueña RF

    更新日期:1996-04-12 00:00:00

  • Peripheral nitric oxide signaling directly blocks inflammatory pain.

    abstract::Pain is a classical sign of inflammation, and sensitization of primary sensory neurons (PSN) is the most important mediating mechanism. This mechanism involves direct action of inflammatory mediators such as prostaglandins and sympathetic amines. Pharmacologic control of inflammatory pain is based on two principal str...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Gomes FIF,Cunha FQ,Cunha TM

    更新日期:2020-06-01 00:00:00

  • Formation of cobalt protoporphyrin by chicken hepatocytes in culture. Relationship to decrease of 5-aminolaevulinate synthase caused by cobalt.

    abstract::Cobalt protoporphyrin generated from 5-amino[4-14C]laevulinate by homogenates or primary cultures of chick embryo liver exposed to CoCl2 was found to be radioactivity unextractable by acid/acetone, when extra protein was added. The activity of ferrochelatase was required for formation of cobalt protoporphyrin since in...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sinclair PR,Sinclair JF,Bonkowsky HL,Gibbs AH,De Matteis F

    更新日期:1982-03-15 00:00:00

  • Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake.

    abstract::Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,收录出版


    authors: Yadav VR,Prasad S,Kannappan R,Ravindran J,Chaturvedi MM,Vaahtera L,Parkkinen J,Aggarwal BB

    更新日期:2010-10-01 00:00:00