Induction of caspase-dependent and -independent apoptosis in response to methionine restriction

  • Authors:
    • Shan Lu
    • Sara M. Hoestje
    • Eugene Choo
    • Daniel E. Epner
  • View Affiliations

  • Published online on: February 1, 2003     https://doi.org/10.3892/ijo.22.2.415
  • Pages: 415-420
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Abstract

Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies have demonstrated that methionine restriction causes tumor cell growth arrest and eventually apoptosis. The current studies were undertaken to elucidate the molecular pathways leading to apoptosis induced by methionine restriction. We found that methionine restriction induced formation of oligonucleosomal DNA fragment and cytochrome c release from mitochondria in methionine-dependent PC3 and Hela cells. Methionine restriction also led to cleavage and activation of initiator and effector caspases in Hela cells but not PC3 cells. Furthermore, methionine restriction resulted in cleavage of BID and reduction in Bcl-2 levels in both cell lines. These data suggest that apoptosis induced by methionine restriction is mitochondria-dependent. Methionine restriction induced caspase-independent cell death in PC3 cells, whereas it stimulated caspase-dependent cell death in Hela cells. Cleavage of BID and decreased expression of Bcl-2 upon methionine deprivation may be the underlying mechanism to stimulate release of cytochrome c from mitochondria.

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February 2003
Volume 22 Issue 2

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

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Spandidos Publications style
Lu S, Hoestje SM, Choo E and Epner DE: Induction of caspase-dependent and -independent apoptosis in response to methionine restriction. Int J Oncol 22: 415-420, 2003
APA
Lu, S., Hoestje, S.M., Choo, E., & Epner, D.E. (2003). Induction of caspase-dependent and -independent apoptosis in response to methionine restriction. International Journal of Oncology, 22, 415-420. https://doi.org/10.3892/ijo.22.2.415
MLA
Lu, S., Hoestje, S. M., Choo, E., Epner, D. E."Induction of caspase-dependent and -independent apoptosis in response to methionine restriction". International Journal of Oncology 22.2 (2003): 415-420.
Chicago
Lu, S., Hoestje, S. M., Choo, E., Epner, D. E."Induction of caspase-dependent and -independent apoptosis in response to methionine restriction". International Journal of Oncology 22, no. 2 (2003): 415-420. https://doi.org/10.3892/ijo.22.2.415