A novel apoptosis-like pathway, independent of mitochondria and caspases, induced by curcumin in human lymphoblastoid T (Jurkat) cells

We have shown previously [E, Sikora, A Bielak-Zmijewska, K. Piwocka, J. Ski erski, and E. Radziszewska (1997) Biochem. Pharmacol. 54, 899-907] that cur cumin prevents formation of oligonucleosomal DNA fragmentation in rat thymo cytes and human leukemic T lymphocytes Jurkat cells induced to undergo apop tosis. In this paper we show that 50 mu M curcumin by itself induces cell d eath in Jurkat cells, but its symptoms differ from those observed after a s hort ultraviolet (uv) irradiation. Ultraviolet-irradiated Jurkat cells disp layed typical symptoms of apoptosis: morphological changes, internucleosoma l and high-molecular-weight DNA fragmentation, formation of sub-G, fraction s in DNA content frequency histograms, and dissipation of the mitochondrial transmembrane electric potential (Delta psi). In contrast, curcumin-treate d Jurkat cells exhibited DNA splitting into high-, but not low-, molecular- weight fragments. These cells retained their high mitochondrial Delta psi a nd the content of Ca2+ in endoplasmic reticulum stores remained at the leve l typical for untreated cells. The frequency of opening of the mitochondria l permeability transition pores in curcumin-treated cells was decreased com pared to the controls, whereas uv irradiation made these pores completely o pen. Curcumin did not produce any change in the activity of caspase-3, wher eas uv irradiation considerably activated this protease. The morphology of curcumin-treated cells displayed chromatin condensation, which was insensit ive to the caspase inhibitor z-VAD-fmk, but no formation of typical apoptot ic bodies, as was the case after uv irradiation. In contrast to uv-irradiat ed cells, curcumin-treated Jurkat cells considerably increased the level of Bcl-2. It is concluded that the programmed cell death induced by curcumin in Jurkat cells differs from "classical" by the lack of mitochondrial depol arization and of the involvement of caspases. (C) 1999 Academic Press.