324 M. Jenny et al.: slightly diminished in unstimulated PBMC, whereas a dose-dependent inhibition of neopterin formation was observed in mitogen-stimulated PBMC (IC50 = 453 ± 86 µg/ml). Additionally, we measured also dose-dependent inhibitory effects of this aqueous Crinum latifolium extract on cell proliferation of highly metastatic human prostate carcinoma PC3 cells (IC50 = 4.5 ± 0.8 mg/ml), androgen- sensitive prostate adenocarcinoma LNCaP cells (IC50 =2.3 ± 0.1 mg/ml), and benign prostate hyperplasia BPH-1 cells (IC50 = 2.1 ± 0.04 mg/ml). We conclude that both effects, inhibition of tumor cell growth and recovery of immune functions, are important for the antitumor properties of Crinum latifolium. Keywords Introduction Crinum latifolium (L.) • Peripheral blood mononuclear cells • Indoleamine 2,3-dioxygenase • Prostate cells • Proliferation Plants of the genus Crinum (Amaryllidaceae) comprise about 130 species which are pan- tropically distributed and widely used in folk medicine in different geographical regions around the world. Extracts of Crinum species are reported to exert antitumor, immunostimulating, analgesic, antiviral, antibacterial and antifungal effects, which have been mainly attributed to the more than 150 alkaloids of the Amaryllidaceae type present in Crinum species [1, 2]. The Indian species Crinum latifolium (L.) was traditionally used to treat rheumatism, fistula, tumors, earaches, rubefacient, tubercle and whitlow [3, 4]. In Vietnamese and Chinese traditional medicine hot aqueous extracts of Crinum latifolium are used until nowadays because of its antiviral and antitumor activity, especially to treat prostate cancer [5, 6]. Scientific evidence for an antitumor effect of Crinum latifolium constituents emerged from an aqueous extract of Crinum latifolium leaves, which was found to retard growth of chemically induced 20-methylcholanthrene tumors in rats [7]. The same extract was also shown to activate and stimulate T-cell proliferation of human peripheral blood mononuclear cells (PBMC) and also in vivo following treatment of Balb/c mice [8]. Recent in vitro studies in our laboratory showed that hot and cold aqueous extracts of Crinum latifolium were highly active to suppress mitogen- and interferon (IFN)-γ-induced formation of the pteridine derivative neopterin in PBMC [9]. During the Th-1 type immune response, activated cells release large amounts of cytokines such as interleukin-(IL)-2 or IFN-γ. Pro-inflammatory IFN-γ is an important mediator of the innate and adaptive immune response triggering a variety of physiological and cellular responses e.g. induction of high amounts of antimicrobial and cytocidal reactive oxygen species (ROS) by macrophages and other cells [10]. In human macrophages, IFN-γ induces also the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyses the rate- limiting step of tryptophan degradation via the kynurenine pathway, and formation of the immune activation marker neopterin, via induction of the enzyme guanosine-triphosphate- (GTP)-cyclohydrolase [11, 12]. IDO plays a central role in the suppression of intracellular bacteria and viruses during an antimicrobial immune response and also growth of malignant cells, as ongoing tryptophan degradation limits protein biosynthesis due to deprivation of this essential amino acid [13, 14]. More recently, it has been demonstrated in vitro that also T cell proliferation is inhibited efficiently by IDO [15, 16]. Increased Sci Pharm. 2011; 79: 323–335