The BH3-only protein Noxa is stimulated during apoptosis of chronic lymphocytic leukemia cells triggered by M2YN, a new plant-derived extract

  • Authors:
    • Murhaf Zaher
    • Massoud Mirshahi
    • Yusuf Nuraliev
    • Mijgana Sharifova
    • Isabelle Bombarda
    • Jean-Pierre Marie
    • Christian Billard
  • View Affiliations

  • Published online on: Tuesday, July 12, 2011
  • Pages: 965-972
  • DOI: 10.3892/ijo.2011.1121

Abstract

Deficiency of apoptosis is a hallmark of chronic lymphocytic leukemia (CLL) cells. M2Yn is a natural extract from plants of central Asia, identified for its antiangiogenic properties and its ability to block the migration of malignant cells. Here, we report that in vitro treatment of cells derived from CLL patients with M2Yn results in internucleosomal DNA fragmentation, phosphatidylserine externalization, mitochondrial membrane depolarization, caspase-3 activation and cleavage of the caspase substrate PARP-1. The extents of these effects depend on the patients and are mostly comparable to those of flavopiridol or hyperforin, two known plant-derived apoptosis inducers of CLL cells. M2Yn does not modulate Mcl-1 expression, while downregulation of this antiapoptotic protein is involved in the action of flavopiridol. By contrast, M2Yn, like hyperforin, upregulates the Noxa protein, possibly by inhibiting proteasomal activity. This BH3-only protein is known to trigger the activation of the pro-apoptotic protein Bak through displacement of the Mcl-1/Bak complex at the mitochondrial membrane, as actually observed here in M2Yn-treated cells. Our data, therefore, show that M2Yn can induce the caspase-dependent mitochondrial pathway of apoptosis in CLL cells via a mechanism resembling that of hyperforin. Our data also confirm that the BH3-only protein Noxa is a relevant target for CLL therapy.
Journal Cover

October 2011
Volume 39 Issue 4

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

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Zaher, M., Mirshahi, M., Nuraliev, Y., Sharifova, M., Bombarda, I., Marie, J., & Billard, C. (2011). The BH3-only protein Noxa is stimulated during apoptosis of chronic lymphocytic leukemia cells triggered by M2YN, a new plant-derived extract. International Journal of Oncology, 39(4), 965-972.
MLA
Zaher, Mirshahi, Nuraliev, Sharifova, Bombarda, Marie, and Christian Billard. "The BH3-only protein Noxa is stimulated during apoptosis of chronic lymphocytic leukemia cells triggered by M2YN, a new plant-derived extract." International Journal of Oncology International Journal of Oncology 39.4 (2011): 965-972.
Chicago
Zaher, Mirshahi, Nuraliev, Sharifova, Bombarda, Marie, and Christian Billard. "The BH3-only protein Noxa is stimulated during apoptosis of chronic lymphocytic leukemia cells triggered by M2YN, a new plant-derived extract." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 965-972.