共查询到20条相似文献,搜索用时 31 毫秒
1.
S. V. Burov T. V. Yablokova M. Yu. Dorosh Z. P. Shkarubskaya M. Blank N. Epstein M. Fridkin 《Russian Journal of Bioorganic Chemistry》2006,32(5):413-419
Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in vitro. The dependence of the antitumor effect on the length of peptide chain, amino acid sequence, and structure of the N-terminal group was demonstrated. Modification with palmitic acid was found to result in highly active compounds in the case of analogues containing more than ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led to compounds with significantly lower activities. Analogues of luliberin containing a palmitic acid residue and effectively inhibiting the growth of tumor cells in vitro were synthesized. 相似文献
2.
Repair of alkylated DNA: recent advances 总被引:9,自引:0,他引:9
3.
Sabrina Riedl Beate Rinner Helmut Schaider Karl Lohner Dagmar Zweytick 《Biometals》2014,27(5):981-997
Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of β-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity. 相似文献
4.
Suzanne M. Cloonan John J. Keating Desmond Corrigan John E. O’Brien Pierce V. Kavanagh D. Clive Williams Mary J. Meegan 《Bioorganic & medicinal chemistry》2010,18(11):4009-4031
4-Methylthioamphetamine (4-MTA) is recognised as a 3,4-methylenedioxymethamphetamine (MDMA)-like drug of abuse. Such amphetamine-type drugs often contain byproducts of uncontrolled, illegal clandestine synthetic processes. We report the isolation and structural identification of a number of novel pyridines, dihydropyridone and N,N-di(1-aryl-2-propyl) amines as route-specific byproducts associated with clandestine synthesis of 4-MTA and related amphetamines. We report the in vitro cytotoxicity of 4-MTA, its synthesis byproducts together with some structurally related sulfur substituted α-alkyl phenethylamines in cell lines overexpressing human monoamine transporters as well as in a primary neuronal cell line model and a dopaminergic neuroblastoma cell line. 4-MTA along with a number of other structurally related amphetamine derivatives and synthetic impurities were found to be cytotoxic to these cells within pharmacologically defined concentrations implying that 4-MTA is a cytotoxic agent in vitro and therefore might have the potential to be a neurotoxic agent in vivo. 相似文献
5.
Cervia D Martini D Garcia-Gil M Di Giuseppe G Guella G Dini F Bagnoli P 《Apoptosis : an international journal on programmed cell death》2006,11(5):829-843
Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate
Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently
unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived
cell lines. In addition, we provide evidence that euplotin C treatment results in rapid activation of ryanodine receptors,
depletion of Ca2+ stores in the endoplasmic reticulum (ER), the release of cytochrome c from the mitochondria, activation of caspase-12, and activation of caspase-3, leading to apoptosis. Intracellular Ca2+ overload is an early event which induces apoptosis and is parallelled by ER stress and the release of cytochrome c, whereas caspase-12 may be activated by euplotin C at a later stage in the apoptosis pathway. These events, either independently
or concomitantly, lead to the activation of the caspase-3 and its downstream effectors, triggering the cell to undergo apoptosis.
These results demonstrate that euplotin C may be considered for the design of cytotoxic and pro-apoptotic new drugs. 相似文献
6.
Sirsendu JanaMaitrayee Sinha Dalia ChandaTapasi Roy Kalpita BanerjeeSoumyabrata Munshi Birija S. PatroSasanka Chakrabarti 《生物化学与生物物理学报:疾病的分子基础》2011,1812(6):663-673
The study has demonstrated that dopamine induces membrane depolarization and a loss of phosphorylation capacity in dose-dependent manner in isolated rat brain mitochondria during extended in vitro incubation and the phenomena are not prevented by oxyradical scavengers or metal chelators. Dopamine effects on brain mitochondria are, however, markedly prevented by reduced glutathione and N-acetyl cysteine and promoted by tyrosinase present in the incubation medium. The results imply that quinone oxidation products of dopamine are involved in mitochondrial damage under this condition. When PC12 cells are exposed to dopamine in varying concentrations (100-400 μM) for up to 24 h, a pronounced impairment of mitochondrial bio-energetic functions at several levels is observed along with a significant (nearly 40%) loss of cell viability with features of apoptotic nuclear changes and increased activities of caspase 3 and caspase 9 and all these effects of dopamine are remarkably prevented by N-acetyl cysteine. N-acetyl cysteine also blocks nearly completely the dopamine induced increase in reactive oxygen species production and the formation of quinoprotein adducts in mitochondrial fraction within PC12 cells and also the accumulation of quinone products in the culture medium. Clorgyline, an inhibitor of MAO-A, markedly decreases the formation of reactive oxygen species in PC12 cells upon dopamine exposure but has only mild protective actions against quinoprotein adduct formation, mitochondrial dysfunctions, cell death and caspase activation induced by dopamine. The results have indicated that quinone oxidation products and not reactive oxygen species are primarily involved in cytotoxic effects of dopamine and the mitochondrial impairment plays a central role in the latter process. The data have clear implications in the pathogenesis of Parkinson's disease. 相似文献
7.
Y Suzuki C M Liu L P Chen D Ben-Nathan E F Wheelock 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(9):3146-3152
L5178Y lymphoma cells are restrained from progressive growth in peritoneal cell ("in vitro tumor-regressor" PC) cultures prepared from many DBA/2 mice which harbor the tumor cells in the peritoneal cavity in a tumor-dormant state. Treatment of these PC cultures with 'antibodies to murine interferon-gamma (MuIFN-gamma) and murine tumor necrosis factor (MuTNF) but not with antibody to interleukin 2 (IL-2) receptors eliminated the restraint on tumor cell growth and permitted their progressive proliferation. L5178Y cells were found to be resistant to the direct toxic effects of large concentrations (3,000 U/ml) of MuIFN-gamma and of MuTNF, either alone or in combination. Treatment of PC cultures from tumor-dormant mice, in which tumor cells grew progressively ("in vitro tumor-progressor"), but not PC cultures from normal mice, with exogenous MuIFN-gamma resulted in a marked inhibition of tumor cell growth. The MuIFN-gamma-induced cytotoxic activity was cell-mediated since no soluble tumor-cytotoxic factors could be detected in the cultures. MuIFN-gamma induced cytotoxic activity in plastic-adherent peritoneal cell (AD-PC) cultures, but induced no cytotoxic activity in nonadherent-PC cultures unless small numbers (2%) of AD-PC were present, and inclusion of antibody to MuTNF in these mixed PC cultures blocked the development of cytotoxic activity. Antibody to MuTNF also blocked the development of cytotoxic activity in cultures of MuIFN-gamma-treated whole PC and AD-PC from tumor-dormant mice. These results indicate that MuIFN-gamma and MuTNF are both important in restraining tumor cell growth in PC cultures from tumor-dormant mice, and that MuIFN-gamma requires the presence of MuTNF to induce cytotoxic activity in these cultures. 相似文献
8.
Phenelzine, deprenyl, and antioxidants (SOD, catalase, ascorbate, or rutin) reduced the loss of cell viability in differentiated PC12 cells treated with 250 M MPP+, whereas N-acetylcysteine and dithiothreitol did not inhibit cell death. Phenelzine reduced the condensation and fragmentation of nuclei caused by MPP+ in PC12 cells. Phenelzine and deprenyl prevented the MPP+-induced decrease in mitochondrial membrane potential, cytochrome c release, formation of reactive oxygen species, and depletion of GSH in PC12 cells. Phenelzine revealed a scavenging action on hydrogen peroxide and reduced the hydrogen peroxide–induced cell death in PC12 cells, whereas deprenyl did not depress the cytotoxic effect of hydrogen peroxide. Both compounds reduced the iron and EDTA-mediated degradation of 2-deoxy-d-ribose degradation. The results suggest that phenelzine attenuates the MPP+-induced viability loss in PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress. 相似文献
9.
含镉量子点是典型的量子点,近年来受到广泛研究。含镉量子点的潜在毒性是其在生物成像及生物医药方面应用和发展的关键制约因素,因此,对其毒性作用的研究具有重要意义。目前对含镉量子点的体外毒性研究主要集中在人肝癌细胞(HepG2)、神经分泌细胞(PC12)等细胞实验及斑马鱼胚胎体外培养实验。体内毒性研究包括小鼠等动物实验。这些研究证实,量子点对HepG2等细胞系和小鼠、贻贝等动物均具细胞毒性。研究者们普遍认为,量子点是通过释放其组成中的重金属,诱导生物体产生活性氧自由基,进而引发细胞凋亡或自噬,但对量子点的具体毒性作用机制并不完全清楚。该文对含镉量子点的体内和体外毒性研究工作进展进行了综述,包括含镉量子点对肝肾细胞、神经细胞、血液细胞及免疫细胞等体外毒性研究工作,对陆生及水生动物等的体内毒性研究工作,旨在更好、更全面地评估含镉量子点的毒性,为今后对量子点的毒性作用机制研究提供方向,促进含镉量子点在生物医学方面的发展和应用。 相似文献
10.
Xinge Zhang Zhongming Wu Xiujun Gao Shujun Shu Huijie Zhang Zhen Wang Chaoxing Li 《Carbohydrate polymers》2009,77(2):394-401
The objective of this work was to investigate the possibility of chitosan bearing β-cyclodextrin (CDen-g-CS) nanocomplexes for controlled protein release. CDen-g-CS was synthesized by a one-step procedure with N-succinylated chitosan and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin in the presence of the water-soluble carbodiimide. The amount of β-CD grafted was up to 62.1 wt%. In vitro cytotoxicity against NIH 3T3 cells showed that CDen-g-CS was not cytotoxic and no significant difference of cytotoxicity was found between CDen-g-CS groups. Self-assembled nanocomplexes between CDen-g-CS and insulin were in the size range of 190–328 nm, with positive electrical charge (+3.7 to +25.5 mV) and high loading efficiency (37.7%). Insulin release in vitro was affected by the medium pH and the composition of copolymer. These results demonstrated that CDen-g-CS copolymer was a new promising vehicle for controlled protein release. 相似文献
11.
《Free radical research》2013,47(3-6):205-212
6-Hydroxydopamine(6-OHDA) and Merocyanine-540(MC-540) have been used clinically for purging of neuroblastoma cells prior to autologous bone marrow transplantation. Both substances were found to be more toxic against neuroblastoma cells than against hematopoietic stem cells. The more pronounced cytotoxic effects of 6-OHDA against neuroblastoma cells were not caused by its selective uptake; the rapid autooxidation at physiological pH leads to the formation of H,O, already in the incubation medium. Cytotoxic effects were not detected in short-time test systems (4 hour chromium-51 release assay) but only after longer incubation periods. In contrast, MC-540 proved to be toxic almost equally in short- and long-time test systems. 4-Hydroxynonenal(4-HNE) that may be formed in the plasma membrane subsequently to photoactivation of MC-540 was only slightly more toxic to neuroblastoma cells than to hematopoietic cells. Although the use of 6-OHDA and MC-540 in bone marrow purging has some limitations, the sensitivity of neuroblastoma cells against reactive oxygen compounds may be exploited more generally for therapy of this tumor. 相似文献
12.
Spleen cells from DBA/2 mice bearing the DBA/2 P815X mastocytoma for approximately 2 weeks can be stimulated in vitro by mastocytoma cells to generate cytotoxicity measured as 51Cr release from mastocytoma cells in a 4-hr assay. These cytotoxic cells will not kill allogeneic cell lines but will kill a series of first transplant generation syngeneic tumors. T cells are involved in that treatment of the responding or the cytotoxic cell populations with either anti-T or anti-theta antibody + complement will abrogate all cytotoxicity. Anti-Ly 2.1 antibody + complement treatment of either responder cells (prior to the in vitro culture with irradiated tumor cells) or effector cells after culture markedly decreases cytotoxicity whereas treatment with anti-Ly 1.1 was more effective prior to culture compared to its effect on cytotoxic cells per se. These T cells are in the small lymphocyte class and occur either singly or in aggregates. Suppression of antisyngeneic tumor cytotoxicity by antibody inhibits preferentially the expression of cytotoxicity in the aggregate fractions. 相似文献
13.
H Kriegbaum B Benninghoff B H?cker-Shahin W Dr?ge 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(3):899-904
The release of ornithine by macrophages and its correlation with their immunogenicity after treatment with various macrophage-stimulating substances were analyzed. Pristane-elicited peritoneal macrophages (PM) were found to express strong arginase activity and to release L-ornithine into the extracellular space. This activity is strongly reduced within 3 hr after treatment with tetradecanoylphorbol acetate (TPA) but not with lipopolysaccharide (LPS). Resident PM usually express little arginase activity, but this activity is markedly augmented within 24 or 48 hr after treatment with LPS. The release of ornithine by peritoneal cells (PC) (60 to 90% macrophages) was found to be correlated with their immunogenicity as determined by the in vivo immunization for a subsequent in vitro secondary cytotoxic response against minor H antigens. The immunogenicity of pristane-elicited PC is markedly stronger than that of resident PC or TPA-treated, pristane-elicited PC. Moreover, the immunogenicity of the resident PC and TPA-treated elicited PC is substantially augmented by the simultaneous injection of ornithine, whereas the immunogenicity of the untreated elicited PC is not further augmented by exogenous ornithine, indicating that the endogenous production of ornithine by the stimulating cells had a strong influence on the resulting immune response. Injection of glutathione into pristane-treated mice also reduces the ornithine production and immunogenicity of the resulting peritoneal exudate cells. The immunogenicity in this case is at least partly reconstituted by application of exogenous ornithine. Our experiments revealed no correlation between the production of ornithine and prostaglandin E2. Prostaglandin E2 production of resident and pristane-elicited PC is not markedly different and is in either case strongly augmented by TPA. Elicited or resident PM which have been incubated for several days in culture release practically no ornithine; but ornithine production can be induced again by incubation for 24 hr with LPS and to some extent also with interferon-gamma. 相似文献
14.
Resistance to killing by tumor necrosis factor in an adipocyte cell line caused by a defect in arachidonic acid biosynthesis 总被引:7,自引:0,他引:7
We have found that TA1-R6, which are resistant to the cytotoxic effects of tumor necrosis factor (TNF) in the presence of cycloheximide (Reid, T. R., Torti, F., and Ringold, G. M. (1989) J. Biol. Chem. 264, 4583-4589), have reduced ability to release arachidonic acid (20:4) from membrane phospholipids in response to either TNF or the calcium ionophore A23187 treatment. However, no defect in the activity of phospholipase A2, the principal enzyme responsible for the release of 20:4 from phospholipids, was observed in these cells. Detailed biochemical characterization of these TNF-resistant cells has revealed that these cells are unable to synthesize 20:4 endogenously because of a defect in delta 6-desaturase, the rate-limiting enzyme of 20:4 biosynthesis. This deficiency leads to a marked decrease in the steady-state levels of 20:4 present in choline-containing phospholipid (PC) and ethanolamine-containing phospholipid (PE). The TA1-R6 cells, however, are capable of incorporating exogenous 20:4 into PC and PE, and when loaded in such manner they become significantly more sensitive to the cytotoxic effects of TNF in the presence of cycloheximide. Therefore, the release of arachidonic acid from phospholipids appears to be a critical element in the signaling pathway utilized by TNF and is essential to the rapid cytotoxic response elicited by TNF in the absence of protein synthesis in wild-type TA1 cells. 相似文献
15.
Sang Y. Lee Becky Slagle-Webb Elias Rizk Akshal Patel Patti A. Miller Shen-Shu Sung James R. Connor 《PloS one》2014,9(9)
The standard chemotherapy for brain tumors is temozolomide (TMZ), however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer to as CC-I. There is a dose-dependent cytotoxic effect of CC-I in TMZ resistant astrocytoma cells. Cell death appears to occur via apoptosis. Following CC-I exposure, there was an increase in astrocytoma cells in the S and G2/M phases. In in vivo athymic (nu/nu) nude mice subcutaneous and intracranial tumor models, CC-I completely inhibited tumor growth without liver or kidney toxicity. Molecular modeling and enzyme activity assays indicate that CC-I selectively inhibits topoisomerase IIα similar to other drugs in its class, but its cytotoxic effects on astrocytoma cells are stronger than these compounds. The cytotoxic effect of CC-I is stronger in cells expressing unmethylated O6-methylguanine methyltransferase (MGMT) but is still toxic to cells with methylated MGMT. CC-I can also enhance the toxic effect of TMZ on astrocytoma when the two compounds are combined. In conclusion, we have identified a compound that is effective against astrocytomas including TMZ resistant astrocytomas in both cell culture and in vivo brain tumor models. The enhanced cytotoxicity of CC-I and the safety profile of this family of drugs could provide an interesting tool for broader evaluation against brain tumors. 相似文献
16.
Jannell V. Bazurto Dipti D. Nayak Tomislav Ticak Milya Davlieva Jessica A. Lee Chandler N. Hellenbrand Leah B. Lambert Olivia J. Benski Caleb J. Quates Jill L. Johnson Jagdish Suresh Patel F. Marty Ytreberg Yousif Shamoo Christopher J. Marx 《PLoS biology》2021,19(5)
Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage.The known formaldehyde stress response systems involve enzymatic detoxification. Here, the authors show that the formaldehyde sensor efgA plays an important role in the endogenous formaldehyde stress response in Methylorubrum extorquens, halting cell growth in response to elevated levels of formaldehyde, and is found almost exclusively in methylotrophic taxa. 相似文献
17.
R.H. Heflich R.M. Hazard L. Lommel J.D. Scribner V.M. Maher J.J. McCormick 《Chemico-biological interactions》1980,29(1):43-56
The cytotoxicity of three structurally-related direct-acting carcinogens, N-acetoxy-2-acetylaminofluorene, N-acetoxy-2-acetylaminophenanthrene and N-acetoxy-4-acetylaminobiphenyl, was compared in normal cells and in excision repair deficient xeroderma pigmentosum cells (XP12BE). All three proved significantly more cytotoxic to the XP cells than to the normal cells. At equicytoxic levels, substantially more residues were initially bound to the DNA of the normal cells than to the XP cells, suggesting that the former are able to remove a large percentage of the DNA bound residues before these can result in cell death. The ability of these cell strains to remove bound residues from DNA, to incorporate thymidine into parental strands of DNA during repair replication, and to recover from potentially lethal damage if held in the non-replicating, density-inhibited Go state was compared as a function of dose and time. The XP12BE cells proved virtually incapable of excision repair of DNA damage induced by these carcinogens and of recovery. In contrast, normal cells recovered from the potentially lethal effects of these three compounds and did so at a rate comparable to their rate of removal of bound residues and of repair synthesis. In the excision-deficient XP12BE cells, DNA adducts induced by N-acetoxy-2-acetylaminophenanthrene proved 3- to 6-fold more cytotoxic than adducts induced by the other two carcinogens. 相似文献
18.
Reiji Kannagi Kinya Koizumi Sachiko Hata-Tanoue Tohru Masuda 《Biochemical and biophysical research communications》1980,96(2):711-718
Rabbit platelets rapidly incorporated methyl groups of [3H] methionine to phosphatidylcholine (PC). Rabbit platelets also incorporated [3H]choline to PC, but the rate of incorporation was far lower than that of [3H]methionine. Further fractionation of labeled PC revealed that a considerable amount of arachidonyl PC was synthesized via the N-methylation pathway. Thrombin stimulation resulted in a release of arachidonic acid from PC, and not from phosphatidylethanolamine (PE). These observations suggest that the N-methylation pathway plays an important role in the intracellular mobilization of arachidonic acid from the PE fraction to the PC fraction, this fraction being more sensitive to the hydrolysis with phospholipase A2 during platelet activation. 相似文献
19.
The glycosidic “high anti” conformation is postulated to be the conformation required by the enzymes adenosine kinase and inosine phosphorylase. Purine analogs that are stable in this conformation are either effective substrates or inhibitors of these enzymes. Ara-adenine is shown to be highly unstable in the high anti conformation. The inactivity of ara-adenine as a substrate for both adenosine kinase and inosine phosphorylase is attributed to its inability to assume the high anti conformation specified by these enzymes. That adenosine itself has a local minima in the high anti conformation, as does inosine and guanosine, is required by its ability to inhibit the synthesis of uridylic acid.The minimal cytotoxic properties of ara-adenine is a consequence of its failure, in normal cells, to be converted to the toxic nucleotide form. The ability of ara-adenine to selectively inhibit DNA viruses means that in DNA virus infected cells the conversion of ara-adenine to ara-AMP is facilitated through a mechanism that does not require a substrate high anti conformation.It is apparent that selective antiviral and anticancer nucleoside analogs may be constructed if their conversion to the toxic nucleotide form is prohibited in normal tissues but allowed in cancer cells or virus infected cells. The basis for the selective effects of ara-adenine is that normal cells require a substrate conformation in which ara-adenine is unstable but that certain neoplastic and viral mechanisms for the conversion of ara-adenine to ara-AMP exist which are able to utilize ara-adenine in its stable syn or anti conformations. 相似文献
20.
Ji Wei Tan Chau Ling Tham Daud A. Israf Sang Hyub Lee Min Kyu Kim 《Neurochemical research》2013,38(3):512-518
l-Glutamate plays a crucial role in neuronal cell death, which is known to be associated with various neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this study, we investigated the protective effects of biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, against l-glutamate-induced cytotoxicity in a PC12 cell line. Exposure of the cells to 10 mM l-glutamate was found to significantly increase cell viability loss and apoptosis, whereas pretreatment with various concentrations of biochanin A attenuated the cytotoxic effects of l-glutamate. Specifically, the pretreatment led to not only decreases in the release of lactate dehydrogenase, the number of apoptotic cells, and the activity of caspase-3 but also an increase in the total glutathione level in the l-glutamate-treated PC12 cells. These results indicate that biochanin A may be able to exert neuroprotective effects against l-glutamate-induced cytotoxicity. Furthermore, our findings also imply that biochanin A may act as an antiapoptotic agent in order to perform its protective function. 相似文献