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Article

Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines

  • Authors:
    • Asami Kon
    • Bo Yuan
    • Tomoyuki Hanazawa
    • Hidetomo Kikuchi
    • Mari Sato
    • Ryota Furutani
    • Norio Takagi
    • Hiroo Toyoda
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan, Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan
  • Pages: 1965-1970
    |
    Published online on: August 5, 2013
       https://doi.org/10.3892/or.2013.2657
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Abstract

In the present study, we investigated the effects of progesterone (Pg) on the growth of A3 and its caspase-8-deficient mutant cell line, I9.2, both of which are subclones of a T-cell-derived leukemic Jurkat cell line that lacks the classic cytoplasmic/nuclear Pg receptor. Pg inhibited the cell growth of both cell lines in a dose- and time-dependent manner to a similar extent, regardless of the status of caspase-8 expression. The activation of caspase-9 and -3 was observed in both cell lines following treatment with 50 µM Pg for 24 h. In addition, the activation of caspase-8 was observed in A3 cells. The addition of the pan-caspase inhibitor Boc-D-FMK, significantly suppressed Pg-triggered cytocidal effects in both types of cells. Moreover, exposure to 50 µM Pg for 48 and 72 h resulted in lactate dehydrogenase leakage characteristic of the disruption of cellular membrane integrity. The function of membrane progesterone receptor α coupled directly with the Gi protein was revealed based on the restoration of Pg-triggered loss of mitochondrial membrane potential in the presence of pertussis toxin, an inhibitor specific for Gi protein. These results suggest that growth suppression accompanied with induction of apoptosis by Pg in both Jurkat clone cells was mediated through mitochondrial membrane disruption followed by the activation of the caspase cascade, as a result of the activation of non-genomic effects. The results of the present study provide novel insight into Pg actions toward its use for clinical application in patients with lymphocytic T cell leukemia.
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Copy and paste a formatted citation
Spandidos Publications style
Kon A, Yuan B, Hanazawa T, Kikuchi H, Sato M, Furutani R, Takagi N and Toyoda H: Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines. Oncol Rep 30: 1965-1970, 2013.
APA
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R. ... Toyoda, H. (2013). Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines. Oncology Reports, 30, 1965-1970. https://doi.org/10.3892/or.2013.2657
MLA
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R., Takagi, N., Toyoda, H."Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines". Oncology Reports 30.4 (2013): 1965-1970.
Chicago
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R., Takagi, N., Toyoda, H."Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines". Oncology Reports 30, no. 4 (2013): 1965-1970. https://doi.org/10.3892/or.2013.2657
Copy and paste a formatted citation
x
Spandidos Publications style
Kon A, Yuan B, Hanazawa T, Kikuchi H, Sato M, Furutani R, Takagi N and Toyoda H: Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines. Oncol Rep 30: 1965-1970, 2013.
APA
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R. ... Toyoda, H. (2013). Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines. Oncology Reports, 30, 1965-1970. https://doi.org/10.3892/or.2013.2657
MLA
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R., Takagi, N., Toyoda, H."Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines". Oncology Reports 30.4 (2013): 1965-1970.
Chicago
Kon, A., Yuan, B., Hanazawa, T., Kikuchi, H., Sato, M., Furutani, R., Takagi, N., Toyoda, H."Contribution of membrane progesterone receptor α to the induction of progesterone-mediated apoptosis associated with mitochondrial membrane disruption and caspase cascade activation in Jurkat cell lines". Oncology Reports 30, no. 4 (2013): 1965-1970. https://doi.org/10.3892/or.2013.2657
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