The growth of SW480 colon cancer cells following the transfection with the human interferon beta (hIFN beta) gene entrapped in cationic multilamellar liposomes was effectively inhibited, but not that of the cells transfected with the gene from which the secretion signal sequence of hIFN beta had been deleted. The amount of hIFN beta secreted in the medium from SW480 cells transfected with hIFN beta gradually increased and became maximum 3 days after the transfection, but no hIFN beta was detected in the medium of the cells transfected with the secretion signal-deleted hIFN beta. These findings indicate that the growth inhibition of SW480 cells after the transfection with hIFN beta was caused by hIFN beta secreted from the transfected cells. At that time, SW480 cells were induced to undergo apoptosis, which was identified by morphological aspects, viz., chromatin condensation, nuclear segmentation, and nucleosomal DNA fragmentation. The hIFN beta-induced apoptosis was found to be linked to the activation of caspases 3 and 8 as evidenced by immunoblot, enzymological, and cell death inhibition analyses. (C) 1999 Academic Press.