We tested the effect of ethanol extracts from Ruscus aculeatus (Asparagaceae) and Pleurotus ostreatus (Agaricales) on the survival and proliferation of the Jurkat cell line, a model of human acute T-cell lymphocytic leukemia. R. aculeatus extracts were toxic to both Jurkat cells and human primary lymphocytes. P. ostreatus extracts were significantly more toxic to Jurkat cells than primary lymphocytes, as seen by LDH release and MTT assays. Annexin-V detection as well as Bax, Bcl-2, Smac/Diablo, and Caspase-8 expression were largely unchanged by P. ostreatus extracts. Cell cycle analysis and CDK-4 expression revealed stop of Jurkat cell proliferation. Interestingly, both extracts cause a strong, dose-dependent decrease in p53 levels in Jurkat cells, consistent with toxicity and cell death occurring via an unknown, non-apoptotic mechanism.