Acyclic carotenoids and their oxidation mixtures inhibit the growth of HL-60 human promyelocytic leukemia cells

Lycopene has been known as a potential food component for cancer prevention, since tomato consumption was shown to be associated with reduced risk of certain cancers. We used HL-60 cells as a model of cancer cells to investigate whether acyclic carotenoids, such as phytoene, phytofluene, and zeta -carotene present in tomatoes, other than lycopene, as well as oxidation mixtures of these carotenoids, are potentially involved in the cancer preventive action of tomatoes. When HL-60 cells were grown in the carotenoid-supplemented medium for 120 hours, zeta -carotene and phytofluene at 10 muM inhibited cell growth to 3.7% and 22.6% of the growth in control culture, respectively, although they were extremely unstable in the culture medium. The oxidation mixture of each carotenoid, which was prepared by incubation in toluene at 37 degreesC for 24 hours, more. strongly inhibited cell growth than each intact carotenoid: The growth inhibition by lycopene was remarkably enhanced by its oxidation before supplementation to the medium. Phytofluene, zeta -carotene, and the oxidation mixture of lycopene induced apoptosis in HL-60 cells during incubation for 24 hours. The addition of alpha -tocopherol to the medium did not eliminate growth inhibition by the oxidation mixture of lycopene. These results suggest that the acyclic carotenoids inhibit cell growth through apoptosis induction and that oxidation products of the carotenoids participate in the growth inhibition.