The Flavonoid Rutin but not the Alkaloid Arborinine Induces Apoptosis in a B-Cell Hybridoma Cell Line

Renata Roseghini; Georgenes Morato Falcão; José Fernando Oliveira Costa; Jorge Clarêncio; Ivana Nascimento; Eudes Velozo; Robert Schaer; Vera Vale; Silvia Lima Costa; Maria de Fátima Dias Costa; Marcienne Tardy; Roberto Meyer; Songelí Menezes Freire

doi:10.1055/s-0029-1185316

Planta Medica, Table of Contents

Planta Med 2009; 75(5): 488-493
DOI: 10.1055/s-0029-1185316

Pharmacology

Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Flavonoid Rutin but not the Alkaloid Arborinine Induces Apoptosis in a B-Cell Hybridoma Cell Line

Renata Roseghini¹ ^, ² , Georgenes Morato Falcão¹ , José Fernando Oliveira Costa³ , Jorge Clarêncio³ , Ivana Nascimento¹ , Eudes Velozo⁴ , Robert Schaer¹ , Vera Vale¹ , Silvia Lima Costa⁵ , Maria de Fátima Dias Costa⁵ , Marcienne Tardy⁶ , Roberto Meyer¹ , Songelí Menezes Freire¹ ^, ²

¹Immunology and Molecular Laboratory (Labimuno), Federal University of Bahia, BA, Brazil
²Escola Bahiana de Medicina e Saúde Pública (EBMSP), BA, Brazil
³Oswaldo Cruz Foundation (CPqGM – FIOCRUZ), BA, Brazil
⁴LAPEMM, Pharmacy Faculty-Federal University of Bahia, BA, Brazil
⁵Laboratory of Neurochemical and Cellular Biology, Federal University of Bahia, BA, Brazil
⁶Inserm, Université de Paris XII, Paris, France

Abstract

The effects of arborinine, an alkaloid extracted from Erthela bahiensis and of rutin, a flavonoid obtained from Dimorphandra mollis (Benth.), Brazilian medicinal plants, on the viability and function of a murine B-cell hybridoma as a tumor model were investigated. The flavonoid rutin at 50 µΜ induced an increase in the number of apoptotic cells of one- to fivefold and reductions in cellular proliferation and monoclonal antibody production. Less but still significant necrosis was also induced by rutin under the same experimental conditions. On the other hand, the alkaloid arborinine exerted no significant effects on the studied parameters.

Key words

Erthela bahiensis - Rutaceae - Dimorphandra mollis - Leguminosae - arborinine - rutin

Full Text

References

1 Reis M S, Mariot A. Diversidade natural e aspectos agronômicos de plantas medicinais. Simões CMO, editor Farmacognosia: da planta ao medicamento. Porto Alegre; Florianópolis, Universidade 1999: 39-41
2 Ng T B, Liu F, Wang Z T. Antioxidative activity of natural products from plants. Life Sci. 2000; 66 709-723
3 Huang Y, Fang Y, Wu J, Dziadyk J M, Zhu X, Sui M, Fan W. Regulation of Vinca alkaloid-induced apoptosis by NF-kappaB/IkappaB pathway in human tumor cells. Mol Cancer Ther. 2004; 3 271-277
4 Geetha V S, Viswanathan S, Kameswaran L. Comparison of total alkaloids of Thylophora indica and disodium cromoglycate on mast cell stabilization. Indian J Pharmacol. 1981; 13 199-201
5 Chen J J, Deady L W, Mackay M F. Synthesis of some acridone alkaloids and related compounds. Tetrahedron. 1997; 53 12717-12728
6 Queener S F, Fujioka H, Nishiyama Y, Furukawa H, Bartlett M S, Smith J W. In vitro activities of acridone alkaloids against Pneumocystis carinii. Antimicrob Agents Chemother. 1991; 35 377-379
7 Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M, Takemura Y, Ju-ichi M, Ito C, Furakawa H. Acridones as inducers of HL‐60 cell differentiation. Leuk Res. 1999; 23 263-269
8 Martinez-Florez S, Gonzallez-Gallego J, Culebras J M, Tuñon M J. Los flavonóides: propiedades y acciones antioxidantes. Nutr Hosp. 2002; XVII‐6 271-278
9 Lorenzi H. Árvores Brasileiras: manual de identificação e cultivo de plantas arbóreas nativas do Brasil. Rio de Janeiro; Plantarum 1949: 175
10 Janbaz K H, Saeed S A, Gilani A H. Protective effect of rutin on paracetamol- and CCl₄-induced hepatotoxicity in rodents. Fitoterapia. 2002; 73 557-563
11 Deschner E E, Ruperto J, Wong G, Newmark H L. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis. 1991; 12 1193-1196
12 Knowles L M, Zigrossi D A, Tauber R A, Hightower C, Milner J A. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer. 2000; 38 116-122
13 Ostrakhovitch E A, Afanas'ev I B. Oxidative stress in rheumathoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators. Biochem Pharmacol. 2001; 62 743-746
14 Roseghini R, Rocha D S, Clarêncio J, Costa S L, Costa M FD, Tardy M, Nascimento I, Schaer R, Velozo E, Meyer R, Freire S M. Flavonoid rutin alters the viability and function of mitogen stimulated splenocytes and thymocytes compared to non-stimulated cells. Immunopharmacol Immunotoxicol. 2007; 29 271-285
15 Roseghini R, Morrerra P RS, Vale V, Pinheiro A M, Costa J, Freire S M, Nascimento I, Schaer R, Velozo E, El-Bachá R, Meyer R. Different effects of arborinine alkaloid obtained from Brazilian Erthela baihensis on spleen and thymus cells stimulated in vitro with different mitogens. Immunopharmacol Immunotoxicol. 2006; 28 361-376
16 Alkan S. Monoclonal antibodies: the story of a discovery that revolutionized science and medicine. Nat Rev Immunol. 2004; 4 153-156
17 Santos C S, Januário A H, Vieira P C, Fernandes J B, Silva M FGF, Pirani J R. Cycloartane triterpenoid and alkaloids from Ameidea spp. J Braz Chem Soc. 1998; 1 39-42
18 Vale V LC, Costa M, Pacheco A, Carminati R, Gomes A P, Regis L F, Barreto L M, Oliveira S C, Meyer R. Evaluation of the immune response cellular profile from mice immunized with Corynebacterium pseudotuberculosis and stimulated by somatic and secreted antigen. São Pedro, SP, Brazil: Annals of XXX Meeting of the Brazilian Society of Immunology 2005: 240
19 Petit P X, Lecouer H, Zorn E, Dauguet C, Mingott B. Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. J Cell Biol. 1995; 130 157-167
20 Middleton E JR, Kandaswami C, Theoharides T C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacol Rev. 2000; 52 673-751
21 Cerqueira F, Cordeiro-da-Silva A, Araújo N, Cidade H, Kijoa A, Nascimento M SJ. Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor. Life Sci. 2003; 73 2321-2334
22 Quader M A, Nutan M TH, Rashid M A. Antitumor alkaloid from Glycosmis pentaphylla. Fitoterapia. 1999; 70 305-307
23 Hirano R, Sasamoto W, Matsumoto A, Itakura H, Igarashi O Y, Kondo K. Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation. J Nutr Sci Vitaminol. 2001; 47 357-362
24 Wei Y-Q, Zhao X, Kariya Y, Fukata H, Teshigawara K, Uchida A. Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res. 1994; 54 4952-4957
25 Hanashiro K, Sunagawa M, Tokeshi Y, Nakasone T, Ohta S, Nakamura M, Kosugi T. Antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit ongoing IgE secretion of rat IgE-producing hybridoma FE‐3 cells. Eur J Pharmacol. 2006; 547 174-183
26 Meliksetian M B, Davtian T K, Chirkowa I V, Alexanian Y T, Ignatova T N. Alterations in immunoglobulin syntesis during adriamycin-induced apoptosis in mouse hybridoma cells. Cell Biol Int. 1997; 21 69-74
27 Vomastek T, Franěk F. Kinetics of development of spontaneous apoptosis in B cell hybridoma cultures. Immunol Lett. 1993; 35 19-24
28 Ündeğ Ü, Aydın S, Başaran A A, Başaran N. The modulating effects of quercetin and rutin on the mitomycin C induced DNA damage. Toxicol Lett. 2004; 151 143-149
29 Yinjun L, Jie J, Weilai X, Xiangming T. Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3mediated cleavage of poly (ADP-ribose) polymerase (PARP). Am J Hematol. 2004; 76 199-204
30 Solis-Maldonado C, Quintanilla-Licea R, Tamez-Guerra R, Rodríguez-Padilla C, Gomez-Flores R. Differential effects of synthetic indoloquinolisines on in vitro rat lymphocyte and macrofage functions. Int Immunopharmacol. 2003; 3 1261-1271

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