Human tissue factor pathway inhibitor-2 induces caspase-mediated apoptosis in a human fibrosarcoma cell line

Apoptosis : an International Journal on Programmed Cell Death
Prakasha Kempaiah, Walter Kisiel

Abstract

Human TFPI-2 is an extracellular matrix-associated Kunitz-type serine proteinase inhibitor. We previously demonstrated that a human fibrosarcoma cell line, HT-1080, does not express TFPI-2, but genetic restoration of TFPI-2 expression in these cells markedly inhibited their growth and metastasis in vivo. In the present study, either full-length recombinant TFPI-2, or its mutated first Kunitz-type domain (R24K KD1), were offered to HT-1080 cells, and the degree of apoptosis assessed by nuclear fragmentation, ethidium bromide and acridine orange staining, fluorescence activated cell sorting, immunoblotting and gene expression profiling. R24K KD1 induced apoptosis in 69% of HT-1080 cells in a 48 h period compared to 39% for TFPI-2, while a KD1 preparation lacking a reactive site arginine/lysine residue (R24Q KD1) produced only an 18% apoptosis rate, suggesting that the observed apoptosis was related to proteinase inhibition. Immunoblotting experiments indicated increased caspase 3 and 9 activation, up-regulation of pro-apoptotic Bax and suppression of anti-apoptotic Bcl-2 protein. Finally, microarray analyses of R24K KD1-treated cells indicated elevated expression of several pro-apoptotic genes and under-expression of anti-apoptot...Continue Reading

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Citations

Jan 3, 2012·Journal of Experimental & Clinical Cancer Research : CR·Qiao ZhangShu L Zhang
Dec 24, 2008·Archives of Biochemistry and Biophysics·Prakasha KempaiahWalter Kisiel
Feb 15, 2013·The Journal of Investigative Dermatology·Cristiana Lo NigroTim Crook
Jan 9, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Sandra GottschlingMichael Meister
May 12, 2012·Toxicon : Official Journal of the International Society on Toxinology·C C DrewesS H P Farsky
Dec 21, 2014·Journal of Molecular Endocrinology·Srividya VasuPeter R Flatt
Mar 7, 2019·Biochemical Society Transactions·Guojie WuRuby H P Law
May 13, 2021·Biological Chemistry·Marion LavergnePascale Reverdiau
Jun 30, 2021·The Journal of Obstetrics and Gynaecology Research·Hiroshi Kobayashi, Shogo Imanaka

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