Planta Med 2011; 77(13): 1482-1488
DOI: 10.1055/s-0030-1270889
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

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

accepted February 10, 2011

Publication Date:
09 March 2011 (online)

Abstract

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.

References

  • 1 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M J. Cancer Statistics, 2009.  CA Cancer J Clin. 2009;  59 225-249
  • 2 Hanahan D, Weinberg R A. The hallmarks of cancer.  Cell. 2000;  100 57-70
  • 3 Malhotra S, Singh A P. A review of pharmacology of phytochemicals from Indian medicinal plants. Available at. http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijam/vol5n1/phyto.xml Accessed January 10, 2011
  • 4 Cragg G M, Newman D J. Nature: a vital source of leads for anticancer drug development.  Phytochem Rev. 2009;  8 313-331
  • 5 Benevides P J C, Sartorellii P, Kato M J. Phenylpropanoids and neolignans from Piper regnellii.  Phytochemistry. 1999;  52 339-343
  • 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
  • 9 Lampe J W. Spicing up a vegetarian diet: chemopreventive effects of phytochemicals.  Am J Clin Nutr. 2003;  78 5795-5835
  • 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
  • 15 Moss G P. Nomenclature of lignans and neolignans (IUPAC recommendations 2000).  Pure Appl Chem. 2000;  72 1493-1523
  • 16 Saleem M, Kim H J, Ali M S, Lee Y S. An update on bioactive plant lignans.  Nat Prod Rep. 2005;  22 696-716
  • 17 Lee K-H, Xiao Z. Lignans in treatment of cancer and other diseases.  Phytochem Rev. 2003;  2 341-362
  • 18 Trédan O, Galmarini C M, Patel K, Tannock I F. Drug resistance and the solid tumor microenvironment.  J Natl Cancer Inst. 2007;  99 1441-1454
  • 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
  • 20 Stewart H L. The cancer investigator.  Cancer Res. 1959;  19 804-818
  • 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
  • 22 Shoemaker R H. The NCI60 human tumour cell line anticancer drug screen.  Nat Rev Cancer. 2006;  6 813-823
  • 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
  • 25 Litchfield J T, Wilcoxson F. A simplified method of evaluating dose-effect experiments.  J Pharmacol Exp Ther. 1949;  96 99-113
  • 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
  • 29 Tabudravu J N, Jaspars M. Anticancer activities of constituents of kava (Piper methysticum).  South Pacific J Nat Sci. 2005;  23 26-29
  • 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
  • 32 Ruiz-Casado A, Garcia M D, Racionero M A. Pulmonary toxicity of 5-fluoracil and oxaliplatin.  Clin Transl Oncol. 2006;  8 624
  • 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
  • 34 Thompson L U. Experimental studies on lignans and cancer.  Baillieres Clin Endocrinol Metab. 1998;  12 691-705
  • 35 Fan H F, Ren Y M, Wu X L, Wang Q A. Synthesis and cytotoxicity of novel benzofuran neolignans derivatives.  J Chem Res. 2010;  34 233-235
  • 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
  • 40 Ward R S. Lignans, neolignans and related compounds.  Nat Prod Rep. 1997;  14 43-74
  • 41 Nitiss J L. Targeting DNA topoisomerase II in cancer chemotherapy.  Nat Rev Cancer. 2009;  9 338-350
  • 42 Baldwin E L, Osheroff N. Etoposide, topoisomerase II and cancer.  Curr Med Chem Anticancer Agents. 2005;  5 363-372

Dr. João Ernesto de Carvalho

Division of Pharmacology and Toxicology
State University of Campinas – CPQBA/UNICAMP

P. O. Box 6171, 13083-970

Campinas, SP

Brazil

Phone: + 55 19 21 39 28 75

Fax: + 55 19 21 39 28 52

Email: carvalho@cpqba.unicamp.br