Journal of Ethnopharmacology 107 (2006) 91–94 Proapoptotic effect of Uncaria tomentosa extracts Laura De Martino a , Jos´ e Luis Silva Martinot b , Silvia Franceschelli a , Arturo Leone a , Cosimo Pizza a , Vincenzo De Feo a,∗ a Dipartimento di Scienze Farmaceutiche, Universit` a degli Studi di Salerno Via Ponte don Melillo, 84084 Fisciano (Salerno), Italy b Laboratorios Hersil s.a., Los Frutales, Lima, Peru Received 27 July 2005; received in revised form 30 January 2006; accepted 15 February 2006 Available online 29 March 2006 Abstract Uncaria tomentosa (“U˜ na de gato”) (Rubiaceae) is widely used in South America for treatment of gastritis, arthritis, cancer and inflammatory conditions. Recent literature reports cytostatic, antiproliferative, anti-inflammatory, mutagenic and anti-mutagenic properties of extracts of the plant. The present study investigates the possible proapoptotic mechanism via the activation of caspase3, in cytostatic effects of root bark extracts of Uncaria tomentosa on three different tumoral cell lines. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Uncaria tomentosa; MCF7; HeLa; SAOS; Apoptosis; Caspase3 1. Introduction Uncaria tomentosa (Willd.) DC. (Rubiaceae), U˜ na de gato or Cat’s Claw, is a woody liana widely spread in the Amazonic forest of Central and South America. Water extracts of the root bark are used in traditional Peruvian medicine for the treatment of cancer, arthritis, gastritis and some epidemic diseases as well as a contraceptive (Rizzi et al., 1993). Phytochemical studies have shown the presence in the plant of tetracyclic and pentacyclic oxindole alkaloids as well as quinovic acid glycosides (Keplinger et al., 1999; Heitzman et al., 2005). Polyhydroxylated triterpenes, flavonoids, procyani- dines (Keplinger et al., 1999; Heitzman et al., 2005) and sterols (Senatore et al., 1989) have also been isolated from the plant. Available literature reports different biological activities of Uncaria tomentosa extracts and/or semi-purified fractions: antibacterial (Kloucek et al., 2005), immunostimulating, antivi- ral, antioxidant, antirheumatic, on receptors M 1 and 5HT 2 , on experimental amnesia in mice (Heitzman et al., 2005). Extracts of the plant produced enhancement of DNA repair (Sheng et al., 2005), and exerted effects on peripheral blood mononu- clear cells (Winkler et al., 2004), on peroxynitrite production by ∗ Corresponding author. Tel.: +39 089 962824; fax: +39 089 962828. E-mail address: defeo@unisa.it (V. De Feo). polymorphonuclear leukocytes (Ostrakovich et al., 1997). Also effects on lymphocyte survival (Akesson et al., 2003), inhibi- tion of TNF production (Sandoval et al., 2000) and in treat- ment of chemotherapy-induced leukopenia in rats (Sheng et al., 2000) have been reported. Giraldo et al. (2003) showed antini- trosative and anti-inflammatory activities of flavonoids of leaves of Uncaria tomentosa. Extracts and chromatographic fractions have been assayed for their mutagenic and anti-mutagenic prop- erties, showing a protective effect in vitro against photomutage- nesis induced in Salmonella typhimurium strains (Rizzi et al., 1993). Sheng et al. (1998) and Riva et al. (2001) reported the antiproliferative effects of Uncaria tomentosa extracts in dif- ferent cellular lines. Sheng et al. (2005) reported that a Cat’s Claw water extract inhibited cell growth without cell death, thus providing enhanced opportunities for DNA repair, resulting in immune stimulation, anti-inflammatory activity and cancer prevention. Akesson et al. (2003) reported that an aqueous extract of Uncaria tomentosa inhibits proliferation of normal mouse T and B lymphocytes, and that this inhibition is not caused by toxicity or by induction of apoptosis and Sandoval et al. (2002) have demonstrated that oral treatment for 3 days with Uncaria tomentosa protects against indomethacin-induced gastritis, and prevents TNF mRNA expression and apoptosis. On the other hand, Sheng et al. (1998, 2000) showed that an 0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2006.02.013