328 M. Jenny et al.: and it appears that antioxidant compounds (represented by a high ORAC value of the extract) and/or specific alkaloids could play a more relevant role. Phytochemical analysis of Crinum species revealed more than 170 different compounds, most of which are alkaloids of the Amaryllidaceae type, which exhibit a wide range of biological activity such as analgesic, central nervous system, antitumor, and antiviral effects [1, 28]. Although chemical analysis of Crinum latifolium alkaloids have been performed mainly on bulbs, which contain the highest concentrations of alkaloids, the presence of alkaloids, especially of the crinane type e.g. crinamine, crinamidine, crinafoline and crinafolidine, were also detected in water extracts of Crinum latifolium leaves [29]. The extract used in this study was standardized to contain 0.3 µg crinamidine/mg of dry extract. With respect to the results obtained in this study, we speculate on a possible involvement of such crinane- type Amaryllidaceae alkaloids, since they have been shown earlier to possess anticancer activity by inducing apoptosis and at the same time exhibit low toxicity to healthy cells, such as mono-nucleated blood cells [30, 31]. Th1-type cytokine IFN-γ induces activation of IDO in macrophages as well as in other cells including tumor cells such as prostate, colorectal, pancreatic and cervical carcinomas, some of which have been shown to constitutively express IDO [32]. Although IFN-γ production and activation of IDO aims to inhibit the growth of malignant cells and should primarily contribute to tumor rejection, IDO also attenuates T-cell proliferation and consequently the immune response. Thus, beside its role in antimicrobial host defense, IDO plays also an important role as an effector mechanism of the antitumor immune response [33, 34]. However, this immunosuppressive aspect of IDO may enable tumor cells to evade and overcome control by the immune system. Thereby, IDO activity could contribute to the development of immunodeficiency – a major reason for disease progression and death, especially in the latter course of cancer. A beneficial effect of IDO suppression on tumor growth by specific inhibitors was shown in various animal models. Friberg et al. demonstrated an enhancing effect of the small molecule inhibitor 1-methyl tryptophan (1MT) on T-cell activity in vitro and additionally, a capacity of 1MT to retard growth of Lewis lung carcinoma (LLC) cells in syngeneic mice [35]. Uyttenhove et al. showed that ectopic expression of IDO by immunogenic mouse tumor cells promotes tumor growth in preimmunized mice, which could partially be reversed by systemic treatment with 1MT [33]. Using the MMTV-neu/HER2 transgenic mouse model of breast cancer, Muller and coworkers showed also that 1MT slightly retarded tumor outgrowth, whereas combinatory treatment with 1MT and paclitaxel or other chemotherapeutics caused rapid regression of established tumors, which was abrogated in athymic or T-cell depleted mice [36]. Further IDO inhibitors such as methylthiohydantoin-tryptophan (MTH-trp) or the phytoalexin brassinin were also shown to exert a similar pattern of antitumor activity [36–38]. In conclusion, the finding of a strong suppressive effect of Crinum latifolium leave extract on IDO activity in stimulated and resting PBMC, may represent a new aspect in the understanding of the antitumor activities of Crinum latifolium. In addition, an inhibitory effect on prostate tumor cells was demonstrated. In the aggregate, both effects, inhibition of tumor cell growth and recovery of immune functions, may contribute to the reported beneficial effects of Crinum latifolium in the treatment of prostate tumors. Further studies are needed to demonstrate whether our in vitro findings can be transferred to the in vivo situation in patients. Sci Pharm. 2011; 79: 323–335