Abstract: Sphingolipid metabolite mimetics and methods of synthesizing them are provided. The sphingolipid metabolite mimetics are shown to be effective at inducing apoptosis in various types of tumor cells. Further, the sphingolipid metabolite mimetics are shown to be effective at sensitizing multiple types of tumor cells to TRAIL-induced apoptosis. Formulations containing one or more sphingolipid metabolite mimetics and, optionally, one or more cell death receptor agonists are provided. Methods of treating cancer in a subject in need thereof are provided using one or more sphingolipid metabolite mimetics.

Abstract: Verticillin A is found to be a potent inhibitor of histone methyltransferases, selective for G9a, GLP, SUV39H1, SUV39H2, MLL1, and NSD2. Methods of using Verticillin A are provided. The Verticillin A can be synthetically produced or it can be isolated from natural sources. Methods if inhibiting one or more histone methyltransferases are provided. In addition, methods are provided for treating diseases or disorders related to overexpression of one or more histone methyltransferases. Exemplary diseases and disorders to be treated include cancer, asthma, HIV, and progeria.

Abstract: Compositions containing epidithiodioxopiprazines and methods of their use are provided. Epidithiodioxopiprazines can be isolated from natural resources or synthesized de novo. Moreover, epidithiodioxopiprazines, including Verticillin A, are shown to effectively sensitize multiple types of tumor cells to TRAIL-induced apoptosis. In addition, epidithiodioxopiprazines, including Verticillin A, are shown to effectively overcome cancer cell resistance to existing drugs (i.e. Etoposide, Cisplatin, 5-FU and Doxorubicin). Therefore, compositions and methods are provided for use in sensitizing target cancer cells to death receptor- and other anticancer drugs-induced apoptosis. Methods of treating cancer in a subject in need thereof are also provided.