title: Effects of thymoquinone-fatty acid conjugates on cancer cells.
abstract: 4-Acylhydrazones and 6-alkyl derivatives of thymoquinone (TQ) were tested for growth inhibition of human HL-60 leukemia, 518A2 melanoma, KB-V1/Vbl cervix, and MCF-7/Topo breast carcinoma cells. Unsaturated side chains conferred greater activities than equally long saturated chains. The number of C==C bonds was less decisive than chain length. The 6-hencosahexaenyl conjugate 3 e was most active in all resistant tumor cells, with IC(50) (72 h) values as low as 30 nM in MCF-7/Topo cells. The conjugates are likely to operate by mechanisms different from that of TQ. For instance, 3 e induced distinct caspase-independent apoptosis in HL-60 and 518A2 cells concomitant with a loss of mitochondrial membrane potential and a subsequent rise in the levels of reactive oxygen species.
authors.affiliation: Organic Chemistry Laboratory, University of Bayreuth, Universitätsstr. 30, 95440 Bayreuth, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Breyer
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert