Three new indole alkaloids, shearinines D, E, and F (1-3), together with the known shearinine A (4) were isolated from the marine-derived strain of the fungus Penicillium janthinellum Biourge. The chemical structures of 1-4 were established by 2D NMR and HREIMS data. Shearinines A, D, and E induce apoptosis in human leukemia HL-60 cells, and shearinine E also inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells in a soft agar.