Enhancement of stress-induced apoptosis in B-lineage cells by caspase-9 inhibitor.

Blood
Nisha ShahTucker W Lebien

Abstract

We have established human B-lineage (BLIN) acute lymphoblastic leukemia cell lines that retain a dependency on fibroblast monolayers for survival and proliferation. Eight hours following removal from adherent cell contact BLIN cells undergo a decrease in mitochondrial transmembrane potential and an increase in annexin V binding. Unexpectedly, the caspase-9 inhibitor (C9i) benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone enhanced the appearance of apoptotic cells within 8 hours following removal of BLIN cells from fibroblast monolayers. C9i enhancement of apoptosis was dose dependent and did not occur with irreversible inhibitors of caspases-2, -3, -6, and -8. C9i also enhanced apoptosis in cord blood-derived CD19(+) B-lineage cells (but not myeloid cells) removed from murine stromal cells. Longer exposure (> 18 hours) to C9i culminated in apoptosis in a panel of B-lineage acute lymphoblastic leukemia (ALL) cell lines in the presence or absence of fibroblast monolayers, as well as in 2 proliferating leukemic cell lines (RAMOS and CEM). BLIN-4L cells made deficient in caspase-9 by RNA interference exhibited no resistance to apoptotic signals and actually showed increased apoptotic sensitivity to staurosporine. These collectiv...Continue Reading

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Citations

Jun 30, 2009·Molecular Pharmacology·David HermansonChengguo Xing
Apr 23, 2013·TheScientificWorldJournal·Satoru MurataShin-ichiro Kumita
Aug 9, 2008·Toxicology and Applied Pharmacology·Lucy M ElphickGeorge E N Kass
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May 10, 2006·British Journal of Haematology·Ayalew TefferiAnimesh Pardanani
Oct 5, 2010·Biochimica Et Biophysica Acta·Hyo-Soon JeongSsang-Goo Cho
May 26, 2016·Journal of the American Chemical Society·Tanmoy SahaPinaki Talukdar
Dec 10, 2016·Journal of the American Chemical Society·Tanmoy SahaPinaki Talukdar
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark E LasburyChao-Hung Lee

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