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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2012

Open Access 01-12-2012 | Research article

Antitumor activity and macrophage nitric oxide producing action of medicinal herb, Crassocephalum crepidioides

Authors: Koh Tomimori, Shinji Nakama, Ryuichiro Kimura, Kazumi Tamaki, Chie Ishikawa, Naoki Mori

Published in: BMC Complementary Medicine and Therapies | Issue 1/2012

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Abstract

Background

Crassocephalum crepidioides, a plant distributed in Okinawa Islands, is known in folk medicine; however, its anticancer activity has not been investigated. The aim of this study was to determine the in vitro and in vivo antitumor activities of C. crepidioides on murine Sarcoma 180 (S-180) and related molecular mechanisms.

Methods

The antitumor effect of C. crepidioides was evaluated in S-180-cell-bearing mice. Cell growth was assessed using a colorimetric assay. Nitrite and nitrate levels were measured by colorimetry. The expression levels of inducible NO synthase (iNOS) in murine RAW264.7 macrophages was assessed by reverse transcriptase-polymerase chain reaction. Activation of iNOS promoter was detected by reporter gene. Activation of nuclear factor-κB (NF-κB) was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling was analyzed using inhibitors of NF-κB and dominant-negative mutants, and Western blot analysis.

Results

C. crepidioides extract delayed tumor growth in S-180-bearing mice. However, it did not inhibit S-180 cell growth in vitro. Supernatant of cultured C. crepidioides-stimulated RAW264.7 macrophages was cytotoxic to S-180 cells. This cytotoxicity was associated with nitric oxide (NO) production. NF-κB signaling pathway was crucial for the transcriptional activation of iNOS gene. Isochlorogenic acid, a component of C. crepidioides, induced NF-κB activation and iNOS expression.

Conclusions

The results highlight the oncolytic and immunopotentiation properties of C. crepidioides mediated through NF-κB-induced release of NO from macrophages.
Appendix
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Literature
1.
Kongsaeree PK, Prabpai S, Sriubolmas N, Vongvein C, Wiyakrutta S: Antimalarial dihydroisocoumarins produced by Geotrichum sp., an endophytic fungus of Crassocephalum crepidioides. J Nat Prod. 2003, 66: 709-711. 10.1021/np0205598.CrossRefPubMed
2.
Yen GC, Chen HY, Peng HH: Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants. Food Chem Toxicol. 2001, 39: 1045-1053. 10.1016/S0278-6915(01)00053-9.CrossRefPubMed
3.
Aniya Y, Koyama T, Miyagi C, Miyahira M, Inomata C, Kinoshita S, Ichiba T: Free radical scavenging and hepatoprotective actions of the medicinal herb, Crassocephalum crepidioides from the Okinawa Islands. Biol Pharm Bull. 2005, 28: 19-23. 10.1248/bpb.28.19.CrossRefPubMed
4.
Clancy RM, Abramson SB: Nitric oxide: a novel mediator of inflammation. Proc Soc Exp Biol Med. 1995, 210: 93-101.CrossRefPubMed
5.
Ishiyama M, Miyazono Y, Sasamoto K, Ohkura Y, Ueno K: A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. Talanta. 1997, 44: 1299-1305. 10.1016/S0039-9140(97)00017-9.CrossRefPubMed
6.
Brockman JA, Scherer DC, McKinsey TA, Hall SM, Qi X, Lee WY, Ballard DW: Coupling of a signal response domain in IκBα to multiple pathways for NF-κB activation. Mol Cell Biol. 1995, 15: 2809-2818.CrossRefPubMedPubMedCentral
7.
McKinsey TA, Brockman JA, Scherer DC, Al-Murrani SW, Green PL, Ballard DW: Inactivation of IκBβ by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-κB. Mol Cell Biol. 1996, 16: 2083-2090.CrossRefPubMedPubMedCentral
8.
Geleziunas R, Ferrell S, Lin X, Mu Y, Cunningham ET, Grant M, Connelly MA, Hambor JE, Marcu KB, Greene WC: Human T-cell leukemia virus type 1 Tax induction of NF-κB involves activation of the IκB kinase α (IKKα) and IKKβ cellular kinases. Mol Cell Biol. 1998, 18: 5157-5165.CrossRefPubMedPubMedCentral
9.
Iha H, Kibler KV, Yedavalli VRK, Peloponese J-M, Haller K, Miyazato A, Kasai T, Jeang K-T: Segregation of NF-κB activation through NEMO/IKKγ by Tax and TNFα: implications for stimulus-specific interruption of oncogenic signaling. Oncogene. 2003, 22: 8912-8923. 10.1038/sj.onc.1207058.CrossRefPubMed
10.
Crosby MB, Svenson J, Gilkeson GS, Nowling TK: A novel PPAR response element in the murine iNOS promoter. Mol Immunol. 2005, 42: 1303-1310. 10.1016/j.molimm.2004.12.009.CrossRefPubMed
11.
Suzuki T, Hirai H, Murakami T, Yoshida M: Tax protein of HTLV-1 destabilizes the complexes of NF-κB and IκB-α and induces nuclear translocation of NF-κB for transcriptional activation. Oncogene. 1995, 10: 1199-1207.PubMed
12.
13.
Mori N, Prager D: Transactivation of the interleukin-1α promoter by human T-cell leukemia virus type I and type II Tax proteins. Blood. 1996, 87: 3410-3417.PubMed
14.
Sveinbjørnsson B, Olsen R, Seternes OM, Seljelid R: Macrophage cytotoxicity against murine Meth A sarcoma involves nitric oxide-mediated apoptosis. Biochem Biophys Res Commun. 1996, 223: 643-649. 10.1006/bbrc.1996.0948.CrossRefPubMed
15.
Hibbs JB, Taintor RR, Vavrin Z, Rachlin EM: Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988, 157: 87-94. 10.1016/S0006-291X(88)80015-9.CrossRefPubMed
16.
Stuehr DJ, Nathan CF: Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med. 1989, 169: 1543-1555. 10.1084/jem.169.5.1543.CrossRefPubMed
17.
Nathan C, Xie Q-W: Nitric oxide synthases: roles, tolls, and controls. Cell. 1994, 78: 915-918. 10.1016/0092-8674(94)90266-6.CrossRefPubMed
18.
Xie Q-W, Kashiwabara Y, Nathan C: Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem. 1994, 269: 4705-4708.PubMed
19.
Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW, Murphy WJ: Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon γ and lipopolysaccharide. Proc Natl Acad Sci USA. 1993, 90: 9730-9734. 10.1073/pnas.90.20.9730.CrossRefPubMedPubMedCentral
20.
Goldring CEP, Narayanan R, Lagadec P, Jeannin J-F: Transcriptional inhibition of the inducible nitric oxide synthase gene by competitive binding of NF-κB/Rel proteins. Biochem Biophys Res Commun. 1995, 209: 73-79. 10.1006/bbrc.1995.1472.CrossRefPubMed
21.
Kim YM, Paik S-G: Induction of expression of inducible nitric oxide synthase by Taxol in murine macrophage cells. Biochem Biophys Res Commun. 2005, 326: 410-416. 10.1016/j.bbrc.2004.11.043.CrossRefPubMed
22.
Karin M, Ben-Neriah Y: Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Review Immunol. 2000, 18: 621-663. 10.1146/annurev.immunol.18.1.621.CrossRef
23.
Malinin NL, Boldin MP, Kovalenko AV, Wallach D: MAP3K-related kinase involved in NF-κB induction by TNF, CD95 and IL-1. Nature. 1997, 385: 540-544. 10.1038/385540a0.CrossRefPubMed
24.
Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, Gerritsen ME: Novel inhibitors of cytokine-induced IκBα phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem. 1997, 272: 21096-21103. 10.1074/jbc.272.34.21096.CrossRefPubMed
25.
Jeremias I, Kupatt C, Baumann B, Herr I, Wirth T, Debatin KM: Inhibition of nuclear factor κB activation attenuates apoptosis resistance in lymphoid cells. Blood. 1998, 91: 4624-4631.PubMed
26.
Lancaster JR, Hibbs JB: EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci USA. 1990, 87: 1223-1227. 10.1073/pnas.87.3.1223.CrossRefPubMedPubMedCentral
27.
Martin E, Nathan C, Xie Q-W: Role of interferon regulatory factor 1 in induction of nitric oxide synthase. J Exp Med. 1994, 180: 977-984. 10.1084/jem.180.3.977.CrossRefPubMed
28.
Gao J, Morrison DC, Parmely TJ, Russell SW, Murphy WJ: An interferon-γ-activated site (GAS) is necessary for full expression of the mouse iNOS gene in response to interferon-γ and lipopolysaccharide. J Biol Chem. 1997, 272: 1226-1230. 10.1074/jbc.272.2.1226.CrossRefPubMed
29.
Sawada T, Falk LA, Rao P, Murphy WJ, Pluznik DH: IL-6 induction of protein-DNA complexes via a novel regulatory region of the inducible nitric oxide synthase gene promoter: role of octamer binding proteins. J Immunol. 1997, 158: 5267-5276.PubMed
30.
Kim YM, Ko CB, Park YP, Kim YJ, Paik SG: Octamer motif is required for the NF-κB-mediated induction of the inducible nitric oxide synthase gene expression in RAW 264.7 macrophages. Mol Cells. 1999, 9: 99-109.PubMed
31.
Murakami A, Ohigashi H: Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer. 1999, 121: 2357-2363.CrossRef
32.
Ortega MG, Saragusti AC, Cabrera JL, Chiabrando GA: Quercetin tetraacetyl derivative inhibits LPS-induced nitric oxide synthase (iNOS) expression in J774A.1 cells. Arch Biochem Biophys. 2010, 498: 105-110. 10.1016/j.abb.2010.04.014.CrossRefPubMed
33.
Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E: Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007, 2007: 45673-CrossRefPubMedPubMedCentral
Metadata
Title
Antitumor activity and macrophage nitric oxide producing action of medicinal herb, Crassocephalum crepidioides
Authors
Koh Tomimori
Shinji Nakama
Ryuichiro Kimura
Kazumi Tamaki
Chie Ishikawa
Naoki Mori
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2012
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-12-78

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