Abstract:
:Zinc protoporphyrin (ZnPP), a known inhibitor of heme oxygenase-1 (HO-1), has been reported to have anticancer activity in both in vitro and in vivo model systems. While the mechanisms of ZnPP's anticancer activity remain to be elucidated, it is generally believed that ZnPP suppresses tumor growth through inhibition of HO-1 activity. We examined this hypothesis by altering cellular levels of HO-1 in human ovarian (A2780) and prostate cancer (DU145) cells and found that ZnPP inhibits cancer cell viability through an HO-1-independent mechanism. Neither over-expression nor knockdown of HO-1 significantly alters ZnPP's cytotoxicity in human cancer cells, indicating that HO-1 does not mediate ZnPP's inhibitory effect on cancer cell growth. Consistent with these observations, tin protoporphyrin (SnPP), a well-established HO-1 inhibitor, was found to be much less cytotoxic than ZnPP, and docosahexaenoic acid (DHA), an HO-1 inducer, enhanced ZnPP's cytotoxicity. In an effort to define the mechanisms of ZnPP-induced cytotoxicity, we found that ZnPP but not SnPP, diminished β-catenin expression through proteasome degradation and potently suppressed β-catenin-mediated signaling in our model systems. Thus, ZnPP-induced cytotoxicity is independent of HO-1 expression in cancer cells and the Wnt/β-catenin pathway is potentially involved in ZnPP's anticancer activity.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Wang S,Avery JE,Hannafon BN,Lind SE,Ding WQdoi
10.1016/j.bcp.2013.03.011subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1611-8issue
11eissn
0006-2952issn
1873-2968pii
S0006-2952(13)00192-5journal_volume
85pub_type
杂志文章abstract::Corticosteroid esters have been encapsulated into intact erythrocytes and used as an intravenous treatment for adjuvant induced arthritis in the rat. The treatment consisted of injections of the encapsulated steroids with the effects monitored for up to 14 days. On an equivalent weight basis both encapsulated cortisol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90362-3
更新日期:1983-11-15 00:00:00
abstract::PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. S...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.03.008
更新日期:2016-05-01 00:00:00
abstract::Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90591-r
更新日期:1991-10-24 00:00:00
abstract::Boldine ([S]-2,9-dihydroxy-1,10-dimethoxyaporphine) has been shown to exert antioxidant and anti-inflammatory effects. The present study elucidated the protective effect of boldine on catecholamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Dopamine (200 microM) an...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00852-8
更新日期:2002-02-01 00:00:00
abstract::We demonstrated recently that phenethyl isothiocyanate (PEITC), a potent anticarcinogen present in cruciferous vegetables, inhibited P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) and that MRP1 can transport PEITC and/or its metabolites. In this study, we have examined whether PEITC is transported by ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.05.025
更新日期:2005-08-15 00:00:00
abstract::H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2, a broad spectrum neuropeptide growth factor antagonist (antagonist G), is soon to enter a phase I clinical trial for the treatment of small-cell lung cancer (SCLC). The pre-clinical pharmacology of this peptide has revealed that its metabolism proceeds from the C-terminus via deam...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00191-2
更新日期:1995-08-25 00:00:00
abstract::Entrectinib is a new tyrosine kinase inhibitor that was recently approved for the treatment of ROS1-positive metastatic non-small cell lung cancer (NSCLC). In this study, we aimed to characterize its potential to act as a modulator of pharmacokinetic cytostatic resistance and perpetrator of drug interactions. In accum...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114061
更新日期:2020-08-01 00:00:00
abstract::The anti-anginal agent bepridil blocks slow Ca2+ channels in a variety of tissues. Since bepridil accumulates inside cells, the possibility exists that bepridil acts, at least partially, from inside the cell. To test this possibility, we examined the effects of a quaternary ammonium analog of bepridil, methylated bepr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90460-0
更新日期:1986-07-15 00:00:00
abstract::Acid secretion from isolated rabbit gastric parietal cells can be stimulated by gastric secretagogues, histamine (cyclic-AMP pathway) and carbachol (inositol phosphate pathway). Prostaglandins (PG) from E series are potent inhibitors of acid secretion. The intracellular mechanism of this inhibition was examined by usi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90608-n
更新日期:1990-06-15 00:00:00
abstract::The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL-60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of 6-M...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00681-3
更新日期:1998-05-15 00:00:00
abstract::[3H]Morphine, PL-017[prolyl-3,4-3H,D-prolyl,3,4-3H] ([3H]PL-017) and enkephalin-(2-D-penicillamine,5-D-penicillamine)[tyrosyl-2,6-3H] ([3H]DPDPE) were directly cross-linked to mouse brain opiate receptors by an ultraviolet (254 nm) irradiation procedure. [3H]Morphine preferentially and specifically labeled a 58 kDa pr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90458-9
更新日期:1993-10-05 00:00:00
abstract::Free radical-induced damage to lipid and protein constituents of neuronal membranes contributes to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). The development of an effective inhibitor of oxidative stress represents an important goal for the treatment of AD. In this study, th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00374-9
更新日期:2000-09-01 00:00:00
abstract::With the aid of a chiral derivatizing reagent and a sensitive and specific nitrogen-phosphorus gas chromatographic assay, metabolism of para-chloroamphetamine (PCA) enantiomers has been studied following incubation of racemic (RS)-, R(-)- and S(+)-PCA with rabbit liver microsomal preparations. Significant metabolism o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90228-3
更新日期:1982-01-01 00:00:00
abstract::Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies showed that 5-fluorouracil and methionine restriction act synergistically against a variety of tumors. The purpose of the current studies was to determine the molecular mechanism(...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00406-4
更新日期:2003-09-01 00:00:00
abstract::Chronic administration of the beta-adrenergic receptor agonist isoproterenol (5 mg/200 g animal for 10 days) resulted in rat parotid and submandibular gland hypertrophy, and it induced synthesis of a series of proline-rich proteins (PRPs) and glycoproteins. Treated parotid glands additionally exhibit an increase in ac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90277-1
更新日期:1985-12-15 00:00:00
abstract::A newly synthesized compound, 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)]amino-N-(4-chlorocinnamyl )-N-methylbenzylamine (CKA-1306), was found to inhibit cyclic AMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase I (CaMK I) with IC50 values of 1.6+/-0.14 and 2.5+/-0.16 microM, respectiv...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00157-9
更新日期:1998-08-01 00:00:00
abstract::Dichlorodi[U-14C]phenyltrichloroethane ( [14C]DDT), incubated with rat hepatic microsomes and NADPH, produced reactive intermediates which covalently bound to microsomal protein and lipids. In atmospheric oxygen, DDT bound to microsomal protein; however, binding was increased up to approximately 70% by oxygen depletio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90483-0
更新日期:1984-01-15 00:00:00
abstract::The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90509-u
更新日期:1993-08-03 00:00:00
abstract::The chiral inversion properties of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), were compared with those of ibuprofen in rats. After administration of R(-)-[2 alpha-2H]KE-748, S(+)-KE-748 was present in the...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00658-2
更新日期:1997-01-24 00:00:00
abstract::Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent ant...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.12.005
更新日期:2014-03-15 00:00:00
abstract::Flunarizine, a calcium (Ca2+)-entry blocker, selective for vascular tissues, inhibits in a concn-dependent way the contraction of isolated rat caudal artery preparations induced by mediators derived from thrombin-stimulated rat platelets. This inhibition is slow in onset and is of prolonged duration. Specific measurem...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90574-9
更新日期:1983-03-01 00:00:00
abstract::Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in he...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90037-5
更新日期:1982-04-01 00:00:00
abstract::The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90127-9
更新日期:1986-05-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone produced by gastrointestinal tract in response to food ingestion. GLP-1 plays a very important role in the glucose homeostasis by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, inhibiting gastric emptying, reducing appetite an...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.01.013
更新日期:2016-03-15 00:00:00
abstract::Structure-activity studies on a series of analogues of N-(3-methyl-S-(1-pyrrolidinyl carbonyl) butyl)-D-alanine ethyl ester hydrochloride (SC42619) have defined the features of this dipeptide analogue required for observation of thrombin receptor antagonist activity on the human platelet. The affinity for SC42619, and...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90037-l
更新日期:1990-01-15 00:00:00
abstract::Chemokines and their receptors play fundamental roles in many physiological and pathological processes such as leukocyte trafficking, inflammation, cancer and HIV-1 infection. Chemokine-receptor interactions are particularly intricate and therefore require precise orchestration. The flexible N-terminal domain of human...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.08.008
更新日期:2012-11-15 00:00:00
abstract::Aminoglycoside antibiotics induce a lysosomal phospholipidosis in kidney proximal tubules after conventional therapy in animals and man. We have previously demonstrated that these drugs bind to negatively charged phospholipid bilayers at acid pH and inhibit the activity of lysosomal acid phospholipases in vitro and in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90607-0
更新日期:1985-04-01 00:00:00
abstract::The reduction of penicillamine disulfide by reductants in aqueous solutions has been studied and compared with that for captopril disulfide. Whereas near quantitative reduction for captopril disulfide was achieved with tributyl phosphine (200 mM), no detectable penicillamine was formed from penicillamine disulfide. Th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90070-0
更新日期:1987-04-15 00:00:00
abstract::Azatoxin was rationally designed as a DNA topoisomerase II (top2) inhibitor [Leteurtre et al., Cancer Res 52: 4478-4483, 1992] and was also found to inhibit tubulin polymerization. Its cytotoxicity is due to action on tubulin at lower concentrations and on top2 at higher concentrations. At intermediate concentrations,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00047-4
更新日期:1995-05-11 00:00:00
abstract::To assess the relative contributions that the sodium channel blocking activity of propranolol may play in a variety of its therapeutic applications, its effects were examined in vitro with a sodium channel specific 22Na+ uptake system, using rat brain membranes. Propranolol inhibited 22Na+ uptake in the rat brain memb...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90668-2
更新日期:1982-05-01 00:00:00