Expression and activation of apoptosis-related molecules involved in interferon-α-mediated apoptosis in human liver cancer cells

  • Authors:
    • Hirohisa Yano
    • Sachiko Ogasawara
    • Seiya Momosaki
    • Jun Akiba
    • Naoyo Nishida
    • Sakiko Kojiro
    • Hironori Ishizaki
    • Masamichi Kojiro
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/ijo.26.6.1645
  • Pages: 1645-1652
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Abstract

Interferon (IFN)-α directly inhibits proliferation of liver cancer cells by inducing apoptosis, but the molecular mechanisms by which IFN-α induces apoptosis in these cells are not fully understood. We examined the effect of broad spectrum caspase inhibitor, Z-VAD-fmk, and the caspase activation in IFN-α-mediated apoptosis by using 4 liver cancer cell lines that were sensitive or resistant to IFN-α-mediated apoptosis. Involvement of apoptosis-related mitochondrial proteins and Bcl-2 family proteins in IFN-α-mediated apoptosis was further examined in 1 sensitive cell line (KIM-1). The Z-VAD-fmk completely or moderately inhibited IFN-α-mediated apoptosis in the sensitive cells. IFN-α induced time-dependent activation of caspase-3 in the sensitive cells, while the resistant cells showed mild or no activation. Activation of caspase-9, caspase-8, and caspase-7, and the cleavage of poly(ADP-ribose)polymerase were identified in either or both of the sensitive cell lines, but not in the resistant cells. In KIM-1 cells, the release of cytochrome c and Smac/DIABLO from mitochondria to cytosole was confirmed. Meanwhile, Bcl-xL was upregulated, and Bid activation or translocation, or conformational changes of Bax were not identified. In conclusion, our results suggest IFN-α-mediated apoptosis in liver cancer cells involves the mitochondrial apoptotic pathway and is induced by activating various caspases.

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June 2005
Volume 26 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yano H, Ogasawara S, Momosaki S, Akiba J, Nishida N, Kojiro S, Ishizaki H and Kojiro M: Expression and activation of apoptosis-related molecules involved in interferon-α-mediated apoptosis in human liver cancer cells. Int J Oncol 26: 1645-1652, 2005
APA
Yano, H., Ogasawara, S., Momosaki, S., Akiba, J., Nishida, N., Kojiro, S. ... Kojiro, M. (2005). Expression and activation of apoptosis-related molecules involved in interferon-α-mediated apoptosis in human liver cancer cells. International Journal of Oncology, 26, 1645-1652. https://doi.org/10.3892/ijo.26.6.1645
MLA
Yano, H., Ogasawara, S., Momosaki, S., Akiba, J., Nishida, N., Kojiro, S., Ishizaki, H., Kojiro, M."Expression and activation of apoptosis-related molecules involved in interferon-α-mediated apoptosis in human liver cancer cells". International Journal of Oncology 26.6 (2005): 1645-1652.
Chicago
Yano, H., Ogasawara, S., Momosaki, S., Akiba, J., Nishida, N., Kojiro, S., Ishizaki, H., Kojiro, M."Expression and activation of apoptosis-related molecules involved in interferon-α-mediated apoptosis in human liver cancer cells". International Journal of Oncology 26, no. 6 (2005): 1645-1652. https://doi.org/10.3892/ijo.26.6.1645