共查询到20条相似文献,搜索用时 25 毫秒
1.
van der Woude H Boersma MG Alink GM Vervoort J Rietjens IM 《Chemico-biological interactions》2006,160(3):193-203
This study investigates the pro-oxidant activity of 3′- and 4′-O-methylquercetin, two relevant phase II metabolites of quercetin without a functional catechol moiety, which is generally thought to be important for the pro-oxidant activity of quercetin. Oxidation of 3′- and 4′-O-methylquercetin with horseradish peroxidase in the presence of glutathione yielded two major metabolites for each compound, identified as the 6- and 8-glutathionyl conjugates of 3′- and 4′-O-methylquercetin. Thus, catechol-O-methylation of quercetin does not eliminate its pro-oxidant chemistry. Furthermore, the formation of these A-ring glutathione conjugates of 3′- and 4′-O-methylquercetin indicates that quercetin o-quinone may not be an intermediate in the formation of covalent quercetin adducts with glutathione, protein and/or DNA. In additional studies, it was demonstrated that covalent DNA adduct formation by a mixture of [4-14C]-3′- and 4′-O-methylquercetin in HepG2 cells amounted to only 42% of the level of covalent adducts formed by a similar amount of [4-14C]-quercetin. Altogether, these results reveal the effect of methylation of the catechol moiety of quercetin on its pro-oxidant behavior. Methylation of quercetin does not eliminate but considerably attenuates the cellular implications of the pro-oxidant activity of quercetin, which might add to the mechanisms underlying the apparent lack of in vivo carcinogenicity of this genotoxic compound. The paper also presents a new mechanism for the pro-oxidant chemistry of quercetin, eliminating the requirement for formation of an o-quinone, and explaining why methylation of the catechol moiety does not fully abolish formation of reactive DNA binding metabolites. 相似文献
2.
From the coral Galaxea fascicularis, a crude mucus-like extract (MS) and subsequently its purified component (P6) appear to contain a DNase-like activity that
indiscriminately digested λDNA, as well as naked genomic DNAs isolated from a multiple-drug-resistant murine leukemia cell
line, P388/VCR, and a nontransformed liver cell line, BL8L. However, MS and P6 specifically induced in situ DNA digestion
in cultured P388/VCR cells from 30 minutes onward. After 3 days of incubation with MS or P6, DNA degradation coincided with
complete killing of P388/VCR. In situ fluorescent labeling of fragmented DNA revealed that P6 induced apoptosis of P388/VCR
cells, occurring as early at 1.5 hours. By day 3, all the P6-treated leukemia cells were apoptotic. In contrast, P6 caused
neither in situ DNA digestion, nor apoptosis in the untransformed BL8L cells. Whether the DNase-like action of P6 is independent
of or responsible for triggering the intrinsic endonuclease activity in the leukemia cell, thus leading to apoptosis, remains
an object for further research. Nevertheless, the specificity of the apoptotic action of P6 on P388/VCR cells indicates its
potential role in the development of an anticancer agent.
Received July 6, 1998; accepted December 21, 1998 相似文献
3.
Toyofumi Yamaguchi Aki Tomikawa Toshiaki Hirai Takeo Kawaguchi Hiroshi Ohrui Mineo Saneyoshi 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1347-1350
Abstract Antileukemic activity of several analogues containing 2′-deoxy-4′-methylcytidine and its araC counterpart were evaluated against murine leukemic P388 cells in vitro and in vivo. Both compounds showed significant cytostatic activity (both IC50=0.4 μM) in vitro and the former compound administered intraperitoneally at a dose of 3 mg/kg/day × 5 showed high activity (T/C=175%) in vivo. The mechanism of action of these 5′-triphosphates on DNA polymerases in detail will be also described. 相似文献
4.
5.
Aki Tomikawa Masaki Seno Kunie Sato‐Kiyotaki Chizuru Ohtsuki Toshialu Hirai Toyofumi Yamaguchi 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):487-501
Abstract Starting from 2′,3′,5′-tri-O-acetyl-2-iodoadenosine, 9-(β-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine and its 2′(S)-azido counterparts were synthesized in seven steps. These exhibited only moderate growth-inhibitory effects against mouse leukemic P388 cells (IC50 = 13–24 μM), although 5′-triphosphate derivatives showed strong and selective inhibitory action on calf thymus DNA polymerase α, but not on β- and ?-polymerases from eukaryotes. 相似文献
6.
Summary Chlamydocin is a powerfulin vitro antitumoral agent, quickly inactivatedin vivo. A series of cyclic tetrapeptides related to chlamydocin or HC toxin and bearing a bioactive alkylating group on an-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analog was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis--chloroethylnitrosourea on thein vivo P388-induced leukemia model. 相似文献
7.
Malaguarnera L Pilastro MR DiMarco R Scifo C Renis M Mazzarino MC Messina A 《Apoptosis : an international journal on programmed cell death》2003,8(5):539-545
Pyrrolidinedithiocarbamate (PDTC) is a metal chelating compound, which exerts both pro-apoptotic effect and pro-oxidant activity on many cells. Our objective was to investigate whether PDTC was able to interfere with apoptotic process in leukemic and normal bone marrow CD34+ cells. Since hematopoietic growth factors stimulate growth and differentiation and prevent apoptosis, we therefore studied the effect of growth factors pretreatment, such as interleukin-3 and granulocyte-macrophage colony stimulating factor, in human myeloid CD34+ cells to evaluate whether they protect the cells from the apoptotic action of PDTC.We revealed that PDTC exerted an apoptotic effect in leukemic CD34+ cells. This effect was dependent on the ability of this compound to generate the oxidation of cellular glutathion to its disulphide and consequently to induce an intracellular oxidative stress. Hematopoietic growth factors did not protect cells from apoptosis induced by previous treatment with PDTC. The ability of PDTC to induce apoptosis was restricted to acute myelogenous leukaemia CD34+ cells, since normal CD34+ cells were insensitive to the pro-oxidant effect of PDTC.These findings imply that normal cells are equipped with mechanisms by which they respond differently to PDTC effects with respect to leukemic cells. 相似文献
8.
Robert T. Dorr Ph. D. h. James D. Liddil M. S. Bhashyam S. lyengar Ph. D. h. Alan F. List M. D. William A. Remers Ph.D. h. 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1655-1667
Abstract A dual prodrug conjugate between the antimetabolite cytarabine monophosphate and the alkylating agent 2,7-diaminomitosene (derived from mitomycin C), cytaramycin, was synthesized and tested for antileukemic activity in sensitive and resistant tumors. The compound was active against parental L-1210, CCRF-CEM, HL-60 and K-562 leukemia cells but did not overcome resistance in sublines developed for (1) multidrug resistance (L-1210/MDR and K-562-R) or (2) for cytarabine resistance (CCRF-CEM/ARA-C and HL-60/ARA-C). Alkaline DNA elution tests demonstrate a predominance of strand breaking activity due to the cytarabine moiety, and a lesser degree of DNA crosslinking, due to the mitosene moiety. The conjugate was active in mice bearing P-388 leukemia (80% increased lifespan), but was not more effective than mitomycin C alone in mice bearing a cytarabine-resistant L-1210 cell line (38% to 31% increased lifespan). These findings suggest that mitomycin nucleotide conjugates do not overcome resistance to the parent antimetabolites. 相似文献
9.
Jun Fukushima Yoshiyuki Sakano Hiroshi Iwai Yasuo Itoh Masaki Tamura Tsuneo Kobayashi 《Bioscience, biotechnology, and biochemistry》2013,77(5):1423-1424
We studied DNA breakage by phenyl compounds present in foodstuffs in vitro using γDNA and in cultured mammalian cells using RFL and HeLa cells. Strong in vitro activity was detected in o- and p-dihydroxyphenols, but the m-isomer had no activity. The same results were obtained with aminophenols and phenylenediamines. In flavonoids, the 3-OH group seemed to be active in the DNA breakage, in addition to the odiphenol group. Cellular DNA breakage by the compounds was different from their in vitro activity and varied with the cell lines. RFL cells were preferable to HeLa cells for screening for DNA breaking substances, because of their greater sensitivity. 相似文献
10.
Maria Luiza Zeraik Maicon S. Petr?nio Dyovani Coelho Luis Octavio Regasini Dulce H. S. Silva Luiz Marcos da Fonseca Sergio A. S. Machado Vanderlan S. Bolzani Valdecir F. Ximenes 《PloS one》2014,9(10)
Pro-oxidant effects of phenolic compounds are usually correlated to the one-electron redox potential of the phenoxyl radicals. Here we demonstrated that, besides their oxidizability, hydrophobicity can also be a decisive factor. We found that esterification of protocatechuic acid (P0) provoked a profound influence in its pro-oxidant capacity. The esters bearing alkyl chains containing two (P2), four (P4) and seven (P7) carbons, but not the acid precursor (P0), were able to exacerbate the oxidation of trolox, α-tocopherol and rifampicin. This effect was also dependent on the catechol moiety, since neither gallic acid nor butyl gallate showed any pro-oxidant effects. A comparison was also made with apocynin, which is well-characterized regarding its pro-oxidant properties. P7 was more efficient than apocynin regarding co-oxidation of trolox. However, P7 was not able to co-oxidize glutathione and NADH, which are targets of the apocynin radical. A correlation was found between pro-oxidant capacity and the stability of the radicals, as suggested by the intensity of the peak current in the differential pulse voltammetry experiments. In conclusion, taking into account that hydroquinone and related moieties are frequently found in biomolecules and quinone-based chemotherapeutics, our demonstration that esters of protocatechuic acid are specific and potent co-catalysts in their oxidations may be very relevant as a pathway to exacerbate redox cycling reactions, which are usually involved in their biological and pharmacological mechanisms of action. 相似文献
11.
Shuangyi Ren Yi Zhang Yujing Wang Yuejian Lui Wei Wei Xiaohua Huang Wenjuan Mao Yunfei Zuo 《Cell biology international》2010,34(12):1205-1211
The P2X7R (P2X7 receptor) is an ATP‐gated cation channel expressed in normal cells that participates in both cell proliferation and apoptosis. Here, we have confirmed P2X7R expression on murine P388D1 lymphoid neoplasm cells. In addition, ATP‐stimulated P2X7R expression was found to trigger increased intracellular calcium flux. Furthermore, silencing with short hairpin RNA and blocking with P2X7R antibody significantly reduced the metastasis of P388D1 cells to lymph nodes. These results indicate that inhibition of the expression and function of P2X7R attenuates the metastatic ability of murine lymphoid neoplasm cell line P388D1, which represents a new potential target for anti‐metastatic therapy. 相似文献
12.
Satoshi Shuto Hiromichi Ito Takumi Obara Keiji Nakagami Masao Yaso Satoshi Yaginuma 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):437-446
Abstract A novel series of neplanocin analogues, 6′-(3-sn-phosphatidyl)neplanocin As bearing a variety of fatty acyl or alkyl residues in the glyceride moiety (2b-2h), were synthesized by means of phospholipase D-catalyzed transphosphatidylation. Among them, 2b, 2c, and 2e each exhibited significant antitumor effect against P388 leukemia in mice, which evidently surpassed that of parent compound neplanocin A. 相似文献
13.
Toyofumi Yamaguchi Kunie Sato Mineo Saneyoshi 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):529-532
Abstract Several sugar-modified 2-(p-n-butylanilino)-2′-deoxyadenosine analogues, including arabino and 2′(R)-azido-2′-deoxy analogues and their 5′-triphosphates were synthesized. These nucleosides thus obtained exhibited moderate cytotoxicity against P-388 leukemic cells in culture (IC50 = 13–24 μ). In contrast to above results, the 5′-triphosphates have been shown to exert strong and selective inhibitory effects on mammalian DNA polymerase α (Ki= 0.02–0.04 μ). 相似文献
14.
Elisabeth Bernardi Jean-Luc Fauchere Ghanem Atassi Philippe Viallefont Rene Lazaro 《Peptides》1993,14(6):1091-1093
A series of cyclic tetrapeptides bearing the bioactive alkylating group on an ε-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a β-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-β-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model. 相似文献
15.
The electrokinetic properties of doxorubicin (DOX)-resistant (P388/R) and -sensitive (P388/S) murine leukemic cells were studied in a free-flow electrophoresis (FFE) system. The electrophoretic mobilities (EM) of P388/S and P388/R cells were 1.07 and 1.35 x 10(-4) cm2 V-1 s-1, respectively, suggesting a higher net negative charge on the P388/R cells. Neuraminidase treatment decreased the EM of both the P388/S and P388/R cells by 15-20% but had no effect on cellular doxorubicin retention. Total and cell surface sialic acid contents were similar in both the cell lines. Our studies show that no direct correlations may exist among surface charge, cell surface sialic acid content, and doxorubicin retention in DOX-resistant and -sensitive P388 cells; however, differences in cell surface charge between these cell types were used to separate them by preparative FFE. 相似文献
16.
Jun-O Jin Valeria V. Shastina Sung-Won Shin Joo-In Park Sergey A. Avilov Valentin A. Stonik Jong-Young Kwak 《FEBS letters》2009,583(4):697-34
Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and xylose as a third monosaccharide residue. Cucumarioside A2-2 is a pentaoside having glucose as a third monosaccahride unit. We compared the effects of frondoside A and A2-2 for cell death-inducing capability with close attention paid to structure-activity relationships. Both frondoside A and A2-2 strongly induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more potent and rapid than A2-2-induced apoptosis. A2-2-induced but not frondoside A-induced apoptosis was caspase-dependent. This suggests that holothurians may induce apoptosis of leukemic cells caspase-dependently or -independently, depending on the holothurian structure. 相似文献
17.
O. E. Grichenko V. V. Shaposhnikova A. A. Kudryavtsev Yu. N. Korystov 《Biology Bulletin》2004,31(3):221-225
We studied the effect of specific inhibitors of 5- and 12-lipoxygenases as well as the product of cyclooxygenase activity, prostaglandin E2, on proliferation and death of P388 leukemia cells. Inhibition of 5- and 12-lipoxygenases in the cells inhibits proliferation and induces apoptosis. The concentrations of baicalein, an inhibitor of 12-lipoxygenase, and AA861, an inhibitor of 5-lipoxygenase, causing a 50% death rate (LC50) proved to be the same, 50 M. Excessive prostaglandin also inhibited proliferation of the cells and induced apoptosis. The LC50 for prostaglandin E2 was 4 M. The obtained data suggest that apoptosis in P388 cells after lipoxygenase inhibition can be induced by both deficiency of lipoxygenase products and excess of prostaglandins in the cell. 相似文献
18.
Takahiro Matsumoto Seikou Nakamura Souichi Nakashima Masayuki Yoshikawa Katsuyoshi Fujimoto Tomoe Ohta Azumi Morita Rie Yasui Eri Kashiwazaki Hisashi Matsuda 《Bioorganic & medicinal chemistry letters》2013,23(18):5178-5181
The methanolic extract from the dried rhizomes of Curcuma comosa cultivated in Thailand was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extract, three new diarylheptanoids, diarylcomosols I–III, were isolated together with 12 known diarylheptanoids. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The diarylheptanoids inhibited melanogenesis, and several structural requirements of the active constituents for the inhibition were clarified. In particular, (3R)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol exhibited stronger inhibitory effect [IC50 = 0.36 μM] without inducing cytotoxicity. The biological effect was much stronger than that of a reference compound, arbutin [IC50 = 174 μM]. We conclude that diarylheptanoid analogs are promising therapeutic agents for the treatment of skin disorders. 相似文献
19.
The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 μg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities. 相似文献
20.
Markus Hartmann Anne Robert Victor Duarte Bernhard K. Keppler B. Meunier 《Journal of biological inorganic chemistry》1997,2(4):427-432
Three new water-soluble ruthenium porphyrin complexes have been prepared and characterized, one with a cationic ligand, Ru(TMPyP),
and two others with anionic ligands, Ru(p–COOH-PP) and Ru(TPPS). These different complexes and their manganese and iron analogues were tested in vivo as potential
antitumor agents with mice bearing P388 leukemia cells, but these complexes have no significant antitumor activity. The nuclease
activity of Ru(TMPyP) and Ru(p–COOH-PP) was evaluated on supercoiled plasmid DNA after activation by a reducing agent (ascorbate) in the presence of air
or by potassium monopersulfate. No significant activity was evidenced for these ruthenium complexes, in contrast with the
already known nuclease activity of the manganese and iron derivatives of TMPyP.
Received: 15 November 1996 / Accepted: 7 April 1997 相似文献