Inhibition of MMP-2 secretion from brain tumor cells suggests chemopreventive properties of a furanocoumarin glycoside and of chalcones isolated from the twigs of Dorstenia turbinata Bathelemy Ngameni a,b , Mohamed Touaibia a , Ramesh Patnam a , Anissa Belkaid c , Pascal Sonna b , Bonaventure T. Ngadjui b , Borhane Annabi c, * , Rene ´ Roy a, * a De ´partement de Chimie, Universite ´ du Que ´bec a ` Montre ´al, Montreal, 2101 Jeanne-Mance, CP 8888, Succ., Centre-ville, Que., Canada H3C 3P8 b De ´partement de Chimie Organique, Universite ´ de Yaounde ´-1, Yaounde ´, Cameroon c Laboratoire d’Oncologie Mole ´culaire, De ´partement de Chimie, Centre BIOMED, Universite ´ du Que ´bec a ` Montre ´al, Montreal, Que., Canada Received 5 April 2006; received in revised form 22 August 2006 Abstract A furanocoumarin glycoside new named turbinatocoumarin (1) was isolated from the twigs of Dorstenia turbinata. The structure of turbinatocoumarin (1) was assigned as 5-methoxy-3-[3-(b-glucopyranosyloxy)-2-hydroxy-3-methylbutyl]psoralen by means of spectro- scopic analysis. Known compounds have also been isolated from this genus and identified as (2 0 S, 3 0 R)-3 0 -hydroxymarmesin (2), 5-meth- oxy-3-(3-methyl-2,3-dihydroxybutyl)psoralen (3), psoralen (4), kanzonol C (5) which was isolated for the first time from this genus, 4- hydroxylonchocarpin (6), umbelliferone, 4-hydroxy-3-methoxybenzaldehyde and 4-methoxyphenol. As part of our continuing search for potential naturally-occurring antitumor drug candidates, the inhibition of matrix metalloproteinase (MMP)-2 secretion from brain tumor-derived glioblastoma cells by the isolated compounds 1, 3, 5, and 6 was evaluated by zymography and compared to the docu- mented naturally-occurring MMP secretion inhibitors chlorogenic acid (CHL) and epigallocatechin-3-gallate (EGCg). Among the com- pounds tested, the inhibiting MMP secretion concentrations ranged from 0.025 to 250 lM with up to 80% inhibition. The inhibitory activities of compounds 5 and 6 were found comparable to the common reference compounds CHL and EGCg. This suggests that alter- nate sources can be explored and exploited for the availability of chemopreventive molecules. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Dorstenia turbinata; Moraceae; Chalcones; Furanocoumarin glucoside; Turbinatocoumarin; 4-Hydroxylonchocarpin; Psoralen; Kanzonol; Chlorogenic acid; Epigallocatechin-3-gallate; Matrix metalloproteinase; Glioblastoma cells 1. Introduction Tumour progression is often correlated with an overex- pression of matrix metalloproteinases (MMP). These enzymes are produced and secreted as inactive zymogens in the extracellular matrix (ECM) by the tumour cells themselves or by surrounding stromal cells (Seiki and Yana, 2003; Folguera et al., 2004). Several proteases, such as MMP and furin-like serine proteases, are responsible for the specific activation of the latent proMMP forms. Among these, MMP-2, MMP-9, and the membrane-associ- ated type (MT)-1 MMP are thought to play a significant role in several degenerative processes (Annabi et al., 2002a; Desrosiers et al., 2006), and are directly involved in metastatic tumour dispersion and angiogenesis (Itoh et al., 1999; John and Tuszynski, 2001; Lafleur et al., 2001; Annabi et al., 2005). More recently, MMP-2 has also been shown to play important roles in tumour cells 0031-9422/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2006.09.017 * Corresponding authors. Address: De ´partement de Chimie, Universite ´ du Que ´bec a ` Montre ´al, Montreal, 2101 Jeanne-Mance, CP 8888, Succ., Centre-ville, Que., Canada H3C 3P8. Tel.: +1 514 987 3000x7610; fax: +1 514 987 0246 (B. Annabi), Tel.: +1 514 987 3000x2546; fax: +1 514 987 4054 (R. Roy). E-mail addresses: annabi.borhane@uqam.ca (B. Annabi), roy.rene@ uqam.ca (R. Roy). www.elsevier.com/locate/phytochem Phytochemistry 67 (2006) 2573–2579 PHYTOCHEMISTRY