Phytomedicine 12 (2005) 501–505 SHORT COMMUNICATION Senna and the formation of aberrant crypt foci and tumors in rats treated with azoxymethane F. Borrelli, R. Capasso, G. Aviello, G. Di Carlo, A.A. Izzo, N. Mascolo, F. Capasso à Department of Experimental Pharmacology, University of Naples Federico II, Naples, Via D. Montesano 80131 Naples, Italy Abstract Chronicuseofanthraquinonelaxativeshasbeenblamedfortheinductionofhabituationandthedevelopmentofcolonic cancer, but there are no definitive studies which have demonstrated this. To evaluate the carcinogenic potential of anthraquinones, the effect of long-term senna pod extract (SE) treatment on either healthy rats or rats treated with an initiating tumor agent (azoxymethane – AOM) has been studied. SE (30 and 60mg/kg), administered for 110 weeks, did notinducethedevelopmentofaberrantcryptfoci(ACF)andtumorsinhealthyrats.ThedevelopmentofACFandtumors in rats treated with AOM were significantly reduced by SE (30 and 60mg/kg). These results suggest that a chronic SE use does not predispose to colon cancer. By contrast, SE might exert an anti-tumoral activity on rat colon carcinogenesis. Keywords: Anthraquinones; Laxative; Senna; Tumors; Aberrant crypt foci Introduction Anthranoids are a group of naturally occurring laxatives, which are commonly used in clinical practice and as self-medication for chronic constipation (Thorpe, 2001; Gattuso and Kamm, 1994). These laxatives increase intestinal motility and secretion (Capasso and Gaginella, 1997), inducing laxation or a water diar- rhoea. The short-term use of these laxatives is generally safe; they occasionally produce flatulence, meteorism and bowel cramps. However, ease of access to laxatives renders them liable to abuse, and chronic administration can lead to complications like dehydration, hypokalae- mia and pseudomelanosis coli (Capasso and Gaginella, 1997; Xing and Soffer, 2001). In recent years, the risk of colon cancer has been found to be related to constipation and to use of anthraquinone laxatives, but experimental and clinical studies are in disagreement (Brusick and Mengs, 1997). In previous studies we have shown that senna, the anthraquinone drug most frequently employed as a laxative, and cascara, do not influence the carcinogen- esis of rat colon when given for a period of 13–28 weeks (Mascolo et al., 1999; Borrelli et al., 2001). The aim of the present work was to study the carcinogenic potential of senna pod extract (SE), administered orally to rats for a period of 110 weeks. Materials and methods Chemicals Azoxymethane (AOM) was purchased from Sigma (Milan, Italy); SE (from Cassia angustifolia containing about 50% of sennosides B) was obtained from Indena ARTICLE IN PRESS www.elsevier.de/phymed 0944-7113/$-see front matter doi:10.1016/j.phymed.2003.10.008 à Corresponding author. Tel.: +3981678415; fax: +3981678403. E-mail address: fcapasso@unina.it (F. Capasso).