Effects of Thymoquinone–Fatty Acid Conjugates on Cancer Cells

More than the sum of its parts : The seeds of Nigella sativa have been a traditional herbal remedy for ailments such as asthma, diarrhea, and cancer. Their essential oil is rich in polyunsaturated fatty acids and thymoquinone. By linking them covalently, a tremendous boost in anticancer activity can be achieved in resistant tumor cells. magnified image 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 n M 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.