Induction of differentiation and apoptosis by sodium selenite in human colonic carcinoma cells (HT29) Marjory S. Stewart a , Randall L. Davis b , Lance P. Walsh a , Barbara C. Pence a, * a Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA b Department of Nutrition, Texas Tech University, Lubbock, TX 79430, USA Received 6 February 1997; received in revised form 20 March 1997; accepted 20 March 1997 Abstract To explore the mechanism(s) by which selenium (Se) exerts its cancer chemopreventive activity, we studied the effect of selenite (0–100 mM) on cell growth, viability, differentiation, detachment, DNA fragmentation and apoptosis in human colonic carcinoma cells (HT29). Selenite (≥5 mM) decreased cell growth, increased cell detachment and decreased intracel- lular levels of reduced glutathione (GSH), whereas ≥10 mM selenite induced cell differentiation and apoptosis. The chemo- preventive effects of selenite may be related in part to the generation of reactive oxygen species (ROS) resulting from the reaction between selenite and GSH.  1997 Elsevier Science Ireland Ltd. Keywords: Selenite; Glutathione; Colon cancer; Differentiation; Apoptosis 1. Introduction The trace element selenium (Se) has been shown to be cytotoxic in vitro in multiple cell models including Ehrlich ascites [1], mouse leukemic L1210 cells [2] and human mammary tumor cells [3]. Selenium sup- plementation in laboratory animals decreases tumor- igenesis in several tumor models including skin, liver, colon and pancreas [4]. Epidemiological studies sug- gest an inverse relationship between Se intake (and tissue levels of Se) and cancer incidence and mortality rate for several forms of cancer [5]. Clark et al. [6] recently found that the incidence of lung, prostate and colon cancer was lower in Se-supplemented patients. The mechanism(s) by which Se exerts it chemopre- ventive activity is unknown, however, several plausi- ble explanations have been postulated including the role of Se in inducing DNA strand breaks [2,7,8], apoptosis [2,9] and the catalytic properties of Se with glutathione which result in the generation of reactive oxygen species (ROS) [10,11]. The latter is of particular importance because ROS also induce DNA strand breaks [12] and apoptosis [13]. The che- mopreventive activity related to the antioxidant role of Se as a constituent of glutathione peroxidase (GSHPx) is also well established [14]. The chemopreventive effects of Se have been stu- died using various Se compounds, however, selenite has been investigated most extensively and is one of the most effective Se compounds studied. In the pre- sent study, we examined the effect of selenite on growth, viability, differentiation, detachment, DNA fragmentation and apoptosis in human colonic carci- noma cells (HT29). While the effects of selenite on these variables have been reported by several authors Cancer Letters 117 (1997) 35–40 0304-3835/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3835(97)00212-7 * Corresponding author. Tel.: +1 806 7432165; fax: +1 806 7432152.