In vitro and In vivo Anticancer Activity of Extracts, Fractions, and Eupomatenoid-5 Obtained from Piper regnellii Leaves
Giovanna Barbarini Longato1,2
, Larissa Yokota Rizzo1,2
, Ilza Maria de Oliveira Sousa3
, Sirlene Valério Tinti2
, Ana Possenti2
, Glyn Mara Figueira4
, Ana Lúcia Tasca Gois Ruiz2
, Mary Ann Foglio3
, João Ernesto de Carvalho2
1Programa de Pós-graduação em Biologia Celular e Estrutural, Instituto de Biologia, Universidade Estadual de Campinas – UNICAMP, Campinas, SP, Brasil
2Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), UNICAMP, Campinas, SP, Brasil
3Divisão de Fitoquímica, CPQBA, UNICAMP, Campinas, SP, Brasil
4Divisão de Agrotecnologia, CPQBA, UNICAMP, Campinas, SP, Brasil
Further Information
Publication History
received January 17, 2011
revised February 9, 2011
Despite numerous studies with the Piper genus, there are no previous results reporting in vitro or in vivo Piper regnellii (Miq.) C. DC. var. regnellii anticancer activity. The aim of this study was to investigate P. regnellii in vitro and in vivo anticancer activity and further identify its active compounds. In vitro antiproliferative activity was evaluated in 8 human cancer cell lines: melanoma (UACC-62), breast (MCF7), kidney (786–0), lung (NCI-H460), prostate (PC-3), ovary (OVCAR-3), colon (HT29), and leukemia (K-562). Total growth inhibition (TGI) values were chosen to measure antiproliferative activity. Among the cell lines evaluated, eupomatenoid-5 demonstrated better in vitro antiproliferative activity towards prostate, ovary, kidney, and breast cancer cell lines. In vivo studies were carried out with Ehrlich solid tumor on Balb/C mice treated with 100, 300, and 1000 mg/kg of P. regnellii leaves dichloromethane crude extract (DCE), with 30 and 100 mg/kg of the active fraction (FRB), and with 30 mg/kg of eupomatenoid-5. The i. p. administration of DCE, FRB, and eupomatenoid-5 significantly inhibited tumor progression in comparison to control mice (saline). Therefore, this study showed that neolignans of Piper regnellii have promising anticancer activity. Further studies will be undertaken to determine the mechanism of action and toxicity of these compounds.
Key words
Piperaceae -
Piper regnellii (Miq.) C. DC. var. regnellii
- eupomatenoid‐5 - neolignans -
in vitro antiproliferative activity - Ehrlich solid tumor
Supporting Information for this article is available online at
6
Lago J H G, Chen A, Young M C M, Guimarães E F, Oliveira A, Kato M J.
Prenylated benzoic acid derivatives from Piper aduncum L. and P. hostmannianum C. DC. (Piperaceae).
Phytochem Lett.
2009;
2
96-98
7
Tsai I L, Lee F P, Wu C C, Duh C Y, Ishikawa T, Chen J J, Chen Y C, Seki H, Chen I S.
New cytotoxic cyclobutanoid amides, a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens.
Planta Med.
2005;
71
535-542
8
Déciga-Campos M, Rivero-Cruz I, Arriaga-Alba M, Castaneda-Corral G, Angeles-Lopez G E, Navarrete A, Mata R.
Acute toxicity and mutagenic activity of Mexican plants used in traditional medicine.
J Ethnopharmacol.
2007;
110
334-342
10
Selvendiran K, Singh J P V, Sakthisekaran D.
In vivo effect of piperine on serum and tissue glycoprotein levels in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.
Pulm Pharmacol Ther.
2006;
19
107-111
11
Bezerra D P, Pessoa C, Moraes M O, Alencar N M N, Mesquita R O, Lima M W, Pessoa O D L, Chaves J H, Silveira E R, Costa-Lotufo L V.
In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species.
J Appl Toxicol.
2008;
28
599-607
12 Corrêa M P. Dicionário das Plantas Úteis do Brasil e das Exóticas Cultivadas. Rio de Janeiro; Ministério da Agricultura, Instituto Brasileiro de Desenvolvimento Florestal 1984: 373-374
13
Holetz F B, Pessini G L, Sanches N R, Cortez D A G, Nakamura C V, Filho B P D.
Screening of some plants used in the Brazilian folk medicine for the treatment of infectious diseases.
Mem Inst Oswaldo Cruz.
2002;
97
1027-1031
14
Pessini G L, Dias Filho B P, Nakamura C V, Ferreira A G, Cortez D A G.
Neolignanas e análise do óleo essencial das folhas de Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.) Yunck.
Rev Bras Farmacogn.
2005;
15
199-204
19
Nascimento F R F, Cruz G V B, Pereira P V S, Maciel M C G, Silva L A, Azevedo A P S, Barroqueiro E S B, Guerra R N M.
Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.
Life Sci.
2006;
78
2650-2653
21
Sacoman J L, Monteiro K M, Possenti A, Figueira G M, Foglio M A, Carvalho J E.
Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata.
Braz J Med Biol Res.
2008;
41
411-415
23
Fouche G, Cragg G M, Pillay P, Kolesnikova N, Maharaj V J, Senabe J.
In vitro anticancer screening of South African plants.
J Ethnopharmacol.
2008;
119
455-461
24 Lapa A J, Souccar C, Lima-Landman M T R, Castro M S A, Lima T C M. Métodos de avaliação da atividade farmacológica de plantas medicinais. Porto Alegre; Metrópole 2003
26
Vendramini-Costa D B, de Castro I B, Ruiz A L, Marquissolo C, Pilli R A, de Carvalho J E.
Effect of goniothalamin on the development of Ehrlich solid tumor in mice.
Bioorg Med Chem.
2010;
18
6742-6747
27
Chauret D C, Bernard C B, Arnason J T, Durst T, Krishnamurty H G, Sanchez-Vindas P, Moreno N, San Roman L, Poveda L.
Insecticidal neolignans from Piper decurrens.
J Nat Prod.
1996;
59
152-155
28 Longato G B. Atividade anticâncer de extratos brutos e frações ativas obtidos de Piper regnellii (Miq). C. DC. var. regnellii [dissertation]. São Paulo; Universidade Estadual de Campinas 2010
30
Campos P B C, Gama J J T, Pereira L P, Costa-Lotufo L V, Moraes M O, Guimaraes E F, Kato M J, Furlan M, Pessoa C.
Antitumor activity of extracts from Peperomia elongata.
Pharm Biol.
2007;
45
760-765
31
Majdalawieh A F, Carr R I.
In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).
J Med Food.
2010;
13
371-381
33
Verçosa Jr D, Melo M M, Cassali G D, Dantas-Barros A M, Silva Jr P G P.
Influência de Agaricus blazei Murrill sobre o tumor sólido de Ehrlich e linfonodos poplíteos de camundongos.
Arq Bras Med Vet Zootec.
2007;
59
150-154
36
McCann M J, Gill C I R, McGlynn H, Rowland I R.
Role of mammalian lignans in the prevention and treatment of prostate cancer.
Nutr Cancer.
2005;
52
1-14
37
Hedelin M, Lof M, Andersson T M- L, Adlercreutz H, Weiderpass E.
Dietary phytoestrogens and the risk of ovarian cancer in the Women's Lifestyle and Health cohort study.
Cancer Epidemiol Biomarkers.
DOI: 10.1158/1055-9965.EPI-10-0752
, advance online publication 23 November 2010
38
McCann S E, Thompson L U, Nie J, Dorn J, Trevisan M, Shields P G, Ambrosone C B, Edge S B, Li H F, Kasprzak C, Freudenheim J L.
Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study.
Breast Cancer Res Treat.
2010;
122
229-235
39
Huang D M, Guh J H, Chueh S C, Teng C M.
Modulation of anti-adhesion molecule MUC-1 is associated with arctiin-induced growth inhibition in PC-3 cells.
Prostate.
2004;
59
260-267