Abstract：
:Lipophilicity of camptothecins derivatives has been reported to improve the stability of the lactone ring and to favor rapid uptake and intracellular accumulation. Recently, a novel series of lipophilic camptothecins substituted at position 7 was developed, and gimatecan (ST1481) was selected for clinical development on the basis of some favorable features, including potent cytotoxicity and the unique feature of the lack of recognition by breast cancer resistance-associated protein (BCRP). In this work the intrinsic fluorescence properties of this compound were exploited to investigate its intracellular disposition in comparison with the water-soluble camptothecin, topotecan (TPT), in HT-29 colon carcinoma cells and in a subline, HT-29/Mit, selected for resistance to mitoxantrone and overexpressing BCRP. The study was performed at single-cell level by means of microspectrofluorometry and fluorescence image analysis. The results indicated a quite different subcellular localization of TPT ST1481, since TPT localized mainly in mitochondria, whereas gimatecan exhibited a lysosomal localization. An increased persistence of DNA damage in gimatecan-treated cells was consistent with the interpretation that lysosomes represent a store of active drug. In contrast to gimatecan, which showed a similar localization in HT-29 cells and in the mitoxantrone-resistant subline, the cellular pharmacokinetic of TPT was markedly influenced by overexpression of BCRP protein in the resistant subline. In conclusion, the present results indicating a quite different behavior of the two camptothecins suggest that, apart from intracellular accumulation, subcellular distribution plays a role in their cytotoxic potency and contributes to their pharmacological features.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Croce AC,Bottiroli G,Supino R,Favini E,Zuco V,Zunino Fdoi
10.1016/j.bcp.2003.10.034subject
Has Abstractpub_date
2004-03-15 00:00:00pages
1035-45issue
6eissn
0006-2952issn
1873-2968pii
S0006295203008906journal_volume
67pub_type
杂志文章abstract：:The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02104-3
更新日期：1995-12-22 00:00:00
abstract：:The crude mitochondrial fraction of rat brain contains an active dehydrogenase involved in the direct oxidation of gamma-aminobutyric acid. INT (p-iodonitrotetrazolium violet) can serve as an efficient acceptor of electrons in this dehydrogenase reaction. During this oxidation of GABA, ammonia is not produced. In vitr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90553-6
更新日期：1982-10-15 00:00:00
abstract：:Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2005.11.006
更新日期：2006-03-30 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90518-p
更新日期：1990-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.05.020
更新日期：2004-08-15 00:00:00
abstract：:Male ddY mice were given one injection of (1) mercury (mercuric chloride) simultaneously with various doses of selenium (sodium selenite), (2) mercury alone, or (3) various doses of selenium alone. The interaction between mercury and selenium in the liver and kidneys at 1, 5, 24, 120, and 240 hr after administration w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90572-6
更新日期：1985-08-01 00:00:00
abstract：:Epidemiological study has shown strong correlation between the Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. However, the mechanism by which H. pylori induces gastric carcinogenesis is not known. In this review, we focused on the product of cytotoxin-associated gene A (CagA), one of the importa...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.10.022
更新日期：2007-06-01 00:00:00
abstract：:We describe the synthesis and the pharmacological characterization of a new quaternary selective serotonin reuptake inhibitor (SSRI) N-methyl-citalopram (NMC) with periphery restricted action due to its inability to cross the blood brain barrier. NMC recognized and blocked the human platelet serotonin transporter (SER...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.07.035
更新日期：2010-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90380-8
更新日期：1989-02-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90427-7
更新日期：1985-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90104-9
更新日期：1988-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2004.04.024
更新日期：2004-09-15 00:00:00
abstract：:Phenylbutyrate has been shown recently to induce fetal hemoglobin (HbF) production in patients with sickle cell anemia and beta thalassemia. We have now examined related aromatic fatty acids in order to define the range of active structures and identify plausible mechanisms of action. Structure-function analysis revea...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00476-5
更新日期：1996-10-25 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90113-j
更新日期：1991-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.03.004
更新日期：2012-06-15 00:00:00
abstract：:Chlordecone, a polycyclic chlorinated insecticide known as Kepone, inhibited the activities of (Na+-K+)ATPase and Mg2+-ATPase in rat brain synaptosomes. Altered pH and specific activity curves for both enzymes demonstrated significant inhibition by chlordecone in buffered acidic, neutral and alkaline pH ranges. Noncom...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90205-8
更新日期：1983-11-01 00:00:00
abstract：:Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a signifi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02061-6
更新日期：1995-10-26 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2011.05.031
更新日期：2011-11-15 00:00:00
abstract：:Incubation of adriamycin resistant Chinese hamster lung cells with the calmodulin inhibitor trifluoperazine (TFP) resulted in a significant increase in the cellular accumulation of drug. When resistant cells were prelabeled with 32Pi and then treated with TFP, a major increase also occurred in the phosphorylation of a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90686-0
更新日期：1985-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90277-r
更新日期：1990-03-15 00:00:00
abstract：:Sulphation in rats, and other mammals, is carried out by a family of sulphotransferase isoenzymes, which can be further subdivided into oestrogen, hydroxysteroid and phenol sulphotransferases. We have examined the effects of hypophysectomy on the activity and expression of representative members of the three major sul...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00055-5
更新日期：1995-05-17 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.06.027
更新日期：2010-10-15 00:00:00
abstract：:MRS 1754 [N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. This is the least well-defined adenosine receptor subtype, and A(2B) antagonists have potential as antiasthmatic drugs. For use as a radioligand, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00531-7
更新日期：2001-03-15 00:00:00
abstract：:We previously demonstrated that prostaglandin (PG) E₂ stimulates adhesion of mastocytoma P-815 cells (P-815 cells) to the Arg-Gly-Asp (RGD)-enriched matrix via the PGE₂ receptor subtype EP4 [Hatae N, Kita A, Tanaka S, Sugimoto Y, Ichikawa A. Induction of adherent activity in mastocytoma P-815 cells by the cooperation ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.01.010
更新日期：2011-04-01 00:00:00
abstract：:An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2013.12.014
更新日期：2014-04-15 00:00:00
abstract：:Tianeptine is a new tricyclic antidepressant which is metabolized mainly by beta-oxidation of its heptanoic side chain. We determined the effects of tianeptine on the mitochondrial oxidation of natural fatty acids in mice. In vitro, tianeptine (0.5 mM) inhibited by only 32% the formation of beta-oxidation products fro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90580-7
更新日期：1989-11-01 00:00:00
abstract：:As our knowledge on the mechanisms that control cell function increases, more complex signaling pathways and quite intricate cross-talks among regulatory proteins are discovered. Establishing accurate interactions between cellular networks is essential for a healthy cell and different alterations in signaling are know...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2008.08.032
更新日期：2009-02-15 00:00:00
abstract：:Recent experiments from our laboratory have indicated that the inhibitory effect of 3'-azido-3'-deoxythymidine (AZT) on oxidative phosphorylation may occur directly, in addition to being brought about by its inhibition of mtDNA replication. We report here studies on the effect of AZT on adenylate kinase, an enzyme cru...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90564-9
更新日期：1994-10-07 00:00:00
abstract：:The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) has been implicated in the development of various human malignancies, including breast, prostate, ovary, and colon cancer. ERRalpha, bound to a co-activator protein (e.g., peroxisome proliferator receptor gamma co-activator-1alpha, PGC-1alpha), reg...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.05.024
更新日期：2010-09-15 00:00:00
abstract：:We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90039-l
更新日期：1992-07-07 00:00:00
