A Novel Apoptosis-like Pathway, Independent of Mitochondria and Caspases, Induced by Curcumin in Human Lymphoblastoid T (Jurkat) Cells

A Novel Apoptosis-like Pathway, Independent of Mitochondria and Caspases, Induced by Curcumin in... We have shown previously (E. Sikora, A. Bielak-Żmijewska, K. Piwocka, J. Skierski, and E. Radziszewska (1997) Biochem. Pharmacol. 54, 899–907) that curcumin prevents formation of oligonucleosomal DNA fragmentation in rat thymocytes and human leukemic T lymphocytes (Jurkat cells) induced to undergo apoptosis. In this paper we show that 50 μM curcumin by itself induces cell death in Jurkat cells, but its symptoms differ from those observed after a short ultraviolet (uv) irradiation. Ultraviolet-irradiated Jurkat cells displayed typical symptoms of apoptosis: morphological changes, internucleosomal and high-molecular-weight DNA fragmentation, formation of sub-G 1 fractions in DNA content frequency histograms, and dissipation of the mitochondrial transmembrane electric potential (Δψ). In contrast, curcumin-treated Jurkat cells exhibited DNA splitting into high-, but not low-, molecular-weight fragments. These cells retained their high mitochondrial Δψ, and the content of Ca 2+ in endoplasmic reticulum stores remained at the level typical for untreated cells. The frequency of opening of the mitochondrial permeability transition pores in curcumin-treated cells was decreased compared to the controls, whereas uv irradiation made these pores completely open. Curcumin did not produce any change in the activity of caspase-3, whereas uv irradiation considerably activated this protease. The morphology of curcumin-treated cells displayed chromatin condensation, which was insensitive to the caspase inhibitor z-VAD-fmk, but no formation of typical apoptotic bodies, as was the case after uv irradiation. In contrast to uv-irradiated 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 depolarization and of the involvement of caspases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Cell Research Elsevier

A Novel Apoptosis-like Pathway, Independent of Mitochondria and Caspases, Induced by Curcumin in Human Lymphoblastoid T (Jurkat) Cells

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Publisher
Elsevier
Copyright
Copyright © 1999 Academic Press
ISSN
0014-4827
DOI
10.1006/excr.1999.4480
Publisher site
See Article on Publisher Site

Abstract

We have shown previously (E. Sikora, A. Bielak-Żmijewska, K. Piwocka, J. Skierski, and E. Radziszewska (1997) Biochem. Pharmacol. 54, 899–907) that curcumin prevents formation of oligonucleosomal DNA fragmentation in rat thymocytes and human leukemic T lymphocytes (Jurkat cells) induced to undergo apoptosis. In this paper we show that 50 μM curcumin by itself induces cell death in Jurkat cells, but its symptoms differ from those observed after a short ultraviolet (uv) irradiation. Ultraviolet-irradiated Jurkat cells displayed typical symptoms of apoptosis: morphological changes, internucleosomal and high-molecular-weight DNA fragmentation, formation of sub-G 1 fractions in DNA content frequency histograms, and dissipation of the mitochondrial transmembrane electric potential (Δψ). In contrast, curcumin-treated Jurkat cells exhibited DNA splitting into high-, but not low-, molecular-weight fragments. These cells retained their high mitochondrial Δψ, and the content of Ca 2+ in endoplasmic reticulum stores remained at the level typical for untreated cells. The frequency of opening of the mitochondrial permeability transition pores in curcumin-treated cells was decreased compared to the controls, whereas uv irradiation made these pores completely open. Curcumin did not produce any change in the activity of caspase-3, whereas uv irradiation considerably activated this protease. The morphology of curcumin-treated cells displayed chromatin condensation, which was insensitive to the caspase inhibitor z-VAD-fmk, but no formation of typical apoptotic bodies, as was the case after uv irradiation. In contrast to uv-irradiated 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 depolarization and of the involvement of caspases.

Journal

Experimental Cell ResearchElsevier

Published: Jun 15, 1999

References

  • Anti-tumour and antioxidant activity of natural curcuminoids
    Ruby, A.J.; Kuttan, G.; Babu, K.D.; Rajasekharan, K.N.; Kuttan, R.
  • Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells
    Kuo, M.-L.; Huang, T.-S.; Lin, J.-K.
  • The role of calcium in the regulation of apoptosis
    McConkey, D.J.; Orrenius, S.
  • Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization
    Bossy-Wetzel, E.; Newmeyer, D.D.; Green, D.R.
  • Transition from caspase-dependent to caspase-independent mechanisms at the onset of apoptotic execution
    Samejima, K.; Toné, S.; Kottke, T.J.; Enari, M.; Sakahira, H.; Cooke, C.A.; Durrieu, F.; Martins, L.M.; Nagata, S.; Kaufmann, S.H.
  • Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak
    McCarthy, N.J.; Whyte, M.K.B.; Gilbert, C.S.; Evan, G.I.
  • E4orf4, a novel adenovirus death factor that induces p53-independent apoptosis by a pathway that is not inhibited by zVAD-fmk
    Lavoie, J.N.; Nguyen, M.; Marcellus, R.C.; Branton, P.E.; Shore, G.C.
  • Apoptosis in the absence of cytochrome c accumulation in the cytosol
    Tang, D.G.; Li, L.; Zhu, Z.; Joshi, B.
  • Mechanism of anticarcinogenic properties of curcumin: The effect of curcumin on glutathione linked detoxification enzymes in rat liver
    Piper, J.T.; Singhal, S.S.; Salameh, M.S.; Torman, R.T.; Awasthi, Y.C.; Awasthi, S.
  • Expression of Bcl-2 increases intracellular glutathione by inhibiting methionine-dependent GSH efflux
    Meredith, M.J.; Cusick, C.L.; Soltaninassab, S.; Sekhar, K.S.; Lu, S.; Freeman, M.L.

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