Zinc protoporphyrin suppresses cancer cell viability through a heme oxygenase-1-independent mechanism: the involvement of the Wnt/β-catenin signaling pathway.


: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.


Biochem Pharmacol


Biochemical pharmacology


Wang S,Avery JE,Hannafon BN,Lind SE,Ding WQ




Has Abstract


2013-06-01 00:00:00














  • Characterization of the purine-reactive site of the rat testis cytosolic adenylate cyclase.

    abstract::Naturally soluble rat germ cell adenylate cyclase was inhibited by adenosine and the adenosine analogs, 9-beta-D-arabinofuranosyl adenine (AFA) and 2',5'-dideoxyadenosine (DDA), all of which inhibited hormone-sensitive adenylate cyclases at the "P" site. The IC50 values for adenosine and DDA were approximately 0.1 and...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Onoda JM,Braun T,Wrenn SM Jr

    更新日期:1987-06-15 00:00:00

  • Metabolism and mode of selective inhibition of human immunodeficiency virus replication by 3'-azido-2',3'-dideoxy-5-iodouridine and 3'-azido-2',3'-dideoxy-5-bromouridine.

    abstract::3'-Azido-2',3'-dideoxy-5-iodouridine (AzIdUrd) and 3'-azido-2',3'-dideoxy-5-bromouridine (AzBdUrd), previously shown to be potent and selective inhibitors of human immunodeficiency virus replication in vitro were minimally toxic to the uninfected human lymphoid cell line H9 (IC50 = 197 and 590 microM, respectively). B...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: August EM,Qian HY,Birks EM,Thombre UA,Lin TS,Prusoff WH

    更新日期:1993-01-07 00:00:00

  • Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect.

    abstract::The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy: topotecan (Hycantim®), gimatecan (ST1481) and the pro-drug irinotecan (Camptosar®) as well as its active metabolite SN-38 against Leishmania infantum. The activity of c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Prada CF,Alvarez-Velilla R,Balaña-Fouce R,Prieto C,Calvo-Álvarez E,Escudero-Martínez JM,Requena JM,Ordóñez C,Desideri A,Pérez-Pertejo Y,Reguera RM

    更新日期:2013-05-15 00:00:00

  • Inhibition of carcinogen-bioactivating cytochrome P450 1 isoforms by amiloride derivatives.

    abstract::We examined the effects of amiloride derivatives, especially 5-(N-ethyl-N-isopropyl)amiloride (EIPA), on the activity of cytochrome P450 (CYP) 1 isoforms, known to metabolize carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BP), into mutagenic metabolites and whose cellular expression can ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sparfel L,Huc L,Le Vee M,Desille M,Lagadic-Gossmann D,Fardel O

    更新日期:2004-05-01 00:00:00

  • Drastic increase in nitric oxide content in rat brain under halothane anesthesia revealed by EPR method.

    abstract::A drastic increase in nitric oxide (NO) content was revealed by the EPR method in rat brain cortex and cerebellum under halothane anesthesia. The NO scavenger diethyldithiocarbamate sodium salt (DETC) and ferrous citrate were injected into adult rats 30-60 min before anesthesia. Rats were anesthetized by inhalation of...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sjakste N,Baumane L,Meirena D,Lauberte L,Dzintare M,Kalviņs I

    更新日期:1999-12-15 00:00:00

  • The multikinase inhibitor axitinib is a potent inhibitor of human CYP1A2.

    abstract::The tyrosine kinase inhibitors (TKIs) and multikinase inhibitors (MKIs) are oncology drugs of increasing importance that have improved the treatment of multiple tumors types. In some patients these agents produce adverse effects, including pharmacokinetic drug-drug interactions, due to cytochrome P450 (CYP) inhibition...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gu R,Hibbs DE,Ong JA,Edwards RJ,Murray M

    更新日期:2014-03-15 00:00:00

  • Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease.

    abstract::Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Quach ND,Arnold RD,Cummings BS

    更新日期:2014-08-15 00:00:00

  • The in vitro and in vivo depigmenting activity of Coenzyme Q10 through the down-regulation of α-MSH signaling pathways and induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated skin keratinocytes.

    abstract::Coenzyme CoQ10 (CoQ10), a ubiquinone compound, has been reported to inhibit tyrosinase activity and melanin production in melanoma B16F10 cells. However, the molecular mechanism underlying this inhibitory effect is poorly understood. In this paper we aimed to investigate the molecular mechanisms involved in the anti-m...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hseu YC,Ho YG,Mathew DC,Yen HR,Chen XZ,Yang HL

    更新日期:2019-06-01 00:00:00

  • Fifty years of Biochemical Pharmacology: the discipline and the journal.

    abstract::The discipline of biochemical pharmacology emerged in the late 1940s as a result of an increasing emphasis on understanding drug mechanisms at the cellular level. This research approach has contributed significantly to the development of many new drug classes including antihypertensive, antifective, cholesterol loweri...

    journal_title:Biochemical pharmacology

    pub_type: 历史文章,杂志文章


    authors: Enna SJ,Feuerstein GZ,Piette J,Williams M

    更新日期:2008-07-01 00:00:00

  • Selective early loss of polypeptides in liver microsomes of CCl4-treated rats. Relationship to cytochrome P-450 content.

    abstract::Treatment of rats with carbon tetrachloride (CCl4) resulted in early reproducible losses of either one or two specific polypeptides (depending on the inducing agent with which the animals had been treated) in the molecular weight range of the multiple forms of cytochrome P-450. The loss was correlated with a decrease ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Noguchi T,Fong KL,Lai EK,Olson L,McCay PB

    更新日期:1982-03-01 00:00:00

  • Modulation by a human interferon of antitumor effects of cyclophosphamide against a lymphosarcoma in hamsters.

    abstract::Administration to hamsters of a highly purified human leukocyte interferon subtype, IFN-alpha A, obtained by recombinant DNA methods, abolished the efficacy of high doses of cyclophosphamide (2.5 mg/hamster) against the TBD 932 lymphosarcoma. The effect was more pronounced with concomitant than with sequential treatme...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lee SH,Chiu H,Renton KW,Stebbing N

    更新日期:1984-11-01 00:00:00

  • Stimulation of catecholamine biosynthesis via the protein kinase C pathway by endothelin-1 in PC12 rat pheochromocytoma cells.

    abstract::It has been reported that endothelins (ETs) stimulate catecholamine release from chromaffin cells. However, it is not known whether ETs also affect catecholamine biosynthesis. Thus, using a rat pheochromocytoma cell line, PC12, we examined the effects of ETs on catecholamine biosynthesis. The mRNA level and activity o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Takekoshi K,Ishii K,Shibuya S,Kawakami Y,Isobe K,Nakai T

    更新日期:2002-03-01 00:00:00

  • Effects of endosulfan and its metabolites on rat liver mitochondrial respiration and enzyme activities in vitro.

    abstract::Endosulfan (E) is an organochloric insecticide, which is quickly metabolized and eliminated from the body system. Toxic effects of E and its metabolites have been reported. The influence of E and its metabolites, viz. endosulfan sulfate (ES), endosulfan diol (ED) and endosulfan lactone (EL), has been examined on rat l...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dubey RK,Beg MU,Singh J

    更新日期:1984-11-01 00:00:00

  • Structure-activity relationships of alkylamines that inhibit rat liver hydroxysteroid sulfotransferase activities in vitro.

    abstract::Tetraalkylammonium salts having n-propyl to n-amyl side chains inhibited rat liver sulfotransferase (ST) activities toward dehydroepiandrosterone and cortisol, but not ST activity toward 2-naphthol, whereas trialkylamines having ethyl to n-amyl side chains inhibited ST activity toward dehydroepiandrosterone, but not S...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Matsui M,Takahashi M,Miwa Y,Motoyoshi Y,Homma H

    更新日期:1995-03-01 00:00:00

  • Fitting a xenobiotic receptor into cell homeostasis: how the dioxin receptor interacts with TGFbeta signaling.

    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


    authors: Gomez-Duran A,Carvajal-Gonzalez JM,Mulero-Navarro S,Santiago-Josefat B,Puga A,Fernandez-Salguero PM

    更新日期:2009-02-15 00:00:00

  • Expression, maturation, and rhodamine-based fluorescence assay of human cathepsin K expressed in CHO cells.

    abstract::Cathepsin K is a cysteine protease that degrades type I human collagen during bone resorption. We have expressed the recombinant human cathepsin K in Chinese hamster ovary (CHO) cells as a pre-proenzyme and demonstrated that it is processed intracellularly to an active enzyme form and that only the proenzyme form is s...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Claveau D,Riendeau D,Mancini JA

    更新日期:2000-09-15 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

  • Arachidonic acid metabolism in cultured aortic endothelial cells. Effect of cAMP and 3-isobutyl-1-methylxanthine.

    abstract::To investigate the hypothesis that cyclic AMP (cAMP) regulates arachidonic acid metabolism in vascular tissue, we have studied the effects of forskolin (FSK), an activator of adenylate cyclase, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, on hormone-stimulated prostacyclin (PGI2) synthesis in...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Whorton AR,Collawn JB,Montgomery ME,Young SL,Kent RS

    更新日期:1985-01-01 00:00:00

  • Role of tyrosine residues in modulation of claudin-4 by the C-terminal fragment of Clostridium perfringens enterotoxin.

    abstract::The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates the barrier function of claudin-4 via its C-terminal 16 amino acids. In the current study, we investigated the roles of tyrosine residues (Y306, Y310 and Y312) in this region in the modulation of TJs by C-CPE. Single mutations of Y306, Y3...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Harada M,Kondoh M,Ebihara C,Takahashi A,Komiya E,Fujii M,Mizuguchi H,Tsunoda S,Horiguchi Y,Yagi K,Watanabe Y

    更新日期:2007-01-15 00:00:00

  • Bioactivation of N-arylhydroxamic acids by rat hepatic N-acetyltransferase. Detection of multiple enzyme forms by mechanism-based inactivation.

    abstract::Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of part...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wick MJ,Hanna PE

    更新日期:1990-03-15 00:00:00

  • A novel approach for stress-induced gastritis based on paradoxical anti-oxidative and anti-inflammatory action of exogenous 8-hydroxydeoxyguanosine.

    abstract::Reactive oxygen species (ROS) attack guanine bases in DNA and form 8-hydroxydeoxyguanosine (8-OHdG), which has been regarded simply as an oxidative mutagenic by-product. On the other hand, our previous report showed paradoxically ROS attenuating action of generated 8-OHdG. In the current study, both in vitro and in vi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ock CY,Hong KS,Choi KS,Chung MH,Kim Ys,Kim JH,Hahm KB

    更新日期:2011-01-01 00:00:00

  • On the specificity of verapamil as a calcium channel-blocker.

    abstract::The stimulated uptake of 45Ca2+ into incubated cerebrocortical synaptosomes caused by veratrine (75 microM) was blocked by low concentrations of verapamil (0.5-30 microM) which did not prevent or reduce depolarization as judged by efflux of potassium (K+). However, verapamil did not prevent amino acid neutrotransmitte...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Norris DK,Bradford HF

    更新日期:1985-06-01 00:00:00

  • Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.

    abstract::The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lu J,Risbood P,Kane CT Jr,Hossain MT,Anderson L,Hill K,Monks A,Wu Y,Antony S,Juhasz A,Liu H,Jiang G,Harris E,Roy K,Meitzler JL,Konaté M,Doroshow JH

    更新日期:2017-11-01 00:00:00

  • Carboxylesterases in guinea-pig plasma and liver. Tissue specific reactivation by diacetylmonoxime after soman inhibition in vitro.

    abstract::The carboxylesterase activity in both plasma and liver of guinea-pig were separated into three main peaks by chromatofocusing. Two of the three plasma enzymes were retained by affinity chromatography on Affi-Gel Blue (100-200 mesh). Isoelectric points determined by chromatofocusing or isoelectrofocusing were pI 6.1, p...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sterri SH,Fonnum F

    更新日期:1987-11-15 00:00:00

  • Angiotensin metabolism by cerebral microvascular aminopeptidase A.

    abstract::Porcine cerebral microvessels were isolated by differential sieving and centrifugation and were characterized by microscopic examination and marker enzyme enrichment (gamma-glutamyltransferase; EC Purified microvessels contained a membrane-bound enzyme immunologically indistinguishable from renal aminopeptid...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bausback HH,Churchill L,Ward PE

    更新日期:1988-01-15 00:00:00

  • Immunomodulation and enhancement of antitumor activity by co-administration of 1,3-bis(2-chloroethyl)-1-nitrosourea and thymidine.

    abstract::The antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been shown previously to be enhanced markedly by the co-administration of pyrimidine deoxyribonucleosides (Lin and Prusoff, Cancer Res 47: 394-397, 1987). In the present study, we examined the cellular mechanisms underlying the augmentation effe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Poo WJ,Guo X,Haslund B,Mozdziesz DE

    更新日期:1997-03-07 00:00:00

  • Regulation of expression and function of m2 and m4 muscarinic receptors in cultured embryonic chick heart cells by transforming growth factor-beta 1.

    abstract::Incubation of cultured embryonic chicken heart cells with transforming growth factor beta 1 (TGF-beta 1) resulted in a concentration- and time-dependent decrease in the number of muscarinic acetylcholine receptors (mAChR), which reached a maximum by 24 hr. Twenty-four hours following TGF-beta 1 treatment, cm2 and cm4 ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jackson DA,Nathanson NM

    更新日期:1997-08-15 00:00:00

  • Relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) levels in a series of stably transfected cell lines and susceptibility to antitumor quinones.

    abstract::To investigate the importance of NAD(P)H:quinone oxidoreductase 1 (or DT-diaphorase; NQO1) in the bioactivation of antitumor quinones, we established a series of stably transfected cell lines derived from BE human colon adenocarcinoma cells. BE cells have no NQO1 activity due to a genetic polymorphism. The new cell li...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Winski SL,Swann E,Hargreaves RH,Dehn DL,Butler J,Moody CJ,Ross D

    更新日期:2001-06-15 00:00:00

  • Desensitization of neurotensin-induced phosphoinositide hydrolysis in transfected CHO cells.

    abstract::The regulation of neurotensin-induced phosphoinositide turnover was studied in transfected CHO cells expressing the rat neurotensin receptor. Stimulation of these cells with neurotensin resulted in an important, but transient, increase in inositol phosphate cell content. Preincubation of the cells with neurotensin dra...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hermans E,Maloteaux JM

    更新日期:1996-06-28 00:00:00

  • The critical role of porcine cytochrome P450 3A46 in the bioactivation of aflatoxin B1.

    abstract::Aflatoxin B1 (AFB1) is bioactivated by cytochrome P450 (CYP) 3A isoforms in humans to generate the highly reactive epoxide intermediate AFB1-8,9-epoxide (AFBO), causing hepatotoxicity and hepatocarcinoma. Due to the unavoidable contamination in their feed, pigs are more likely to be exposed to AFB1 and indirectly harm...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jiang H,Wu J,Zhang F,Wen J,Jiang J,Deng Y

    更新日期:2018-10-01 00:00:00