Industrial Crops and Products 50 (2013) 661–665 Contents lists available at ScienceDirect Industrial Crops and Products journal h om epage: www.elsevier.com/locate/indcrop Antiproliferative activity and constituents of leaf extracts of Croton sphaerogynus Baill. (Euphorbiaceae) Lucimar B. Motta a,∗ , Cláudia M. Furlan a , Deborah Y.A.C. Santos a , Maria L.F. Salatino a , Giuseppina Negri b , João E. de Carvalho c , Paula A. Monteiro c , Ana Lúcia T.G. Ruiz c , Maria B. Caruzo d , Antonio Salatino a a Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, 277, CEP 05508-090 São Paulo, SP, Brazil b Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil c Divisão de Farmacologia e Toxicologia, CPQBA – CP 6171, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil d Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Diadema, SP, Brazil a r t i c l e i n f o Article history: Received 29 April 2013 Received in revised form 17 June 2013 Accepted 2 August 2013 Keywords: Croton sphaerogynus Euphorbiaceae Antiproliferative activity Diterpenes Podocarpanes Abietanes a b s t r a c t Several Croton species have been used in traditional medicine and contain substances active against cancer, such as diterpenoids and alkaloids. Croton sphaerogynus is a shrub from the Atlantic Rain For- est in southeastern Brazil. The main goal of this study was to characterize the main constituents of the leaf extracts of C. sphaerogynus and evaluate their in vitro antiproliferative activity against tumor cell lines. Hexane, dichloromethane and methanol extracts of leaves were analyzed by GC/MS and eval- uated for their in vitro antiproliferative activity on the cell lines 786-0 (kidney), HT-29 (colon), K562 (leukemia), NCI-ADR/RES (drug resistant ovary), NCI-H460 (lung), MCF-7 (mammary), PC-3 (prostate), OVCAR-3 (ovary), U251 (glioma) and UACC-62 (melanoma). Relevant constituents in dichloromethane and hexane extracts were abietane, podocarpane and clerodane type furano diterpenes. Dicloromethane and hexane extracts exhibited activity against NCI-H460 (GI 50 0.26 g/mL and 0.33 g/mL, respectively) and K562 (GI 50 0.60 g/mL and <0.25 g/mL, respectively). Taking into account all cell lines tested, the dichloromethane extract was shown to have higher activity (mean log GI 50 0.86) than hexane and methanol extracts (mean log GI 50 1.26 and 1.49, respectively). The antiproliferative activity observed in the present work is probably accounted for by the abietane and/or podocarpane diterpenes. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Cancer is among the main causes of death worldwide. Accord- ing to the International Agency for Research on Cancer (IARC), the world impact of cancer more than duplicated in 30 years (WHO, 2009). In Brazil, the National Cancer Institute (INCA) had estimated that over 400,000 new cases of cancer will be reported in 2011, being prostate and lung cancers the most common among men, and breast and uterus among women (INCA, 2009). Among the substances currently used in cancer treatment, over 60% are directly or indirectly derived from plants (Cragg and Newman, 2009), most of them related to alkaloids and terpenoids ∗ Corresponding author. Tel.: +55 1130918065; fax: +55 1130917547. E-mail addresses: lugalll@yahoo.com.br, lbm@gmail.com (L.B. Motta), furlancm@ib.usp.br (C.M. Furlan), dyacsan@ib.usp.br (D.Y.A.C. Santos), mlfsalat@usp.br (M.L.F. Salatino), gnegri@terra.com.br (G. Negri), carvalho je@yahoo.com.br (J.E. de Carvalho), paulaaramon@yahoo.com.br (P.A. Monteiro), analucia@cpqba.unicamp.br (A.L.T.G. Ruiz), mbrcaruzo@hotmail.com (M.B. Caruzo), asalatin@usp.br (A. Salatino). (Gupta et al., 2005). In addition to some well-known plant-derived substances used in chemotherapy (vincristine, vinblastine, taxol and camptothecine), other potentially useful anticancer substances have been found in Annona bullata, Asimina triloba, Cephalotaxus harringtonia, Ochrosia elliptica and Rhizoma zedoarieae (Ram and Kumari, 2001). Croton (Euphorbiaceae) has over 1200 species (Govaerts et al., 2000), ranking it as the 11th largest genus of angiosperm (Frodin, 2004). The species of this genus are found mostly in tropical regions worldwide, but some representatives occur in subtropical and northern temperate areas. The genus presents great morphological diversity and occupies a wide range of habitats. Several Croton species have been used in traditional medicine (Moreno et al., 2009; Perazzo et al., 2010). Croton species contain substances active against cancer, such as diterpenoids (clerodane, furoclerodane and acyclic diterpenes) and alkaloids (e.g. taspine) (Salatino et al., 2007). Shoots of C. hieronymi Griseb. were shown to have strong activity against lung A-549 carcinoma cells, mouse lymphoma and human colon carcinoma (Catalán et al., 2003). The dichloromethane extract of leaves of C. macrobothrys Baill. and C. zambesicus Müll.Arg. showed cytotoxicity against human lung and 0926-6690/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.indcrop.2013.08.008