Brefeldin A-mediated apoptosis requires the activation of caspases and is inhibited by Bcl-2

Hua Guo, Thomas V. Tittle, Hamish Allen, Richard T. Maziarz

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Brefeldin A (BFA) has recently been shown to induce apoptosis in human tumor cells in a p53-independent fashion. In this study, BFA-induced apoptosis was analyzed in the human Jurkat T-cell line. Apoptosis occurred 8 h after treatment with BFA and at concentrations as low as 10 ng/ml and increased with the duration of BFA exposure. Forskolin, an inhibitor of BFA- induced deaggregation of the Golgi-microtubular complex in some cell lines, failed to reverse BFA-mediated apoptosis. Further study of the mechanism of BFA-induced apoptosis was conducted by using a series of peptide protease inhibitors. Complete inhibition of cell death was achieved with benzyloxycarbonyl-Val-Ala-Asp-fluromethylketone, a peptide inhibitor of the caspase protease family, and Z-Asp-Glu-Val-Asp-FMK, a specific inhibitor of caspase-3. Both Acetyl-Tyr-Val-Ala-Asp-chloromethylketone and Acetyl-Tyr- Val-Ala-Asp-aldehyde, selective caspase-1 (interleukin-1β converting enzyme) inhibitors, exerted only partial protection of cells from apoptosis at higher concentrations. Z-Phe-Ala-FMK, a cysteine protease inhibitor lacking aspartate at the P1 position, did not have any impact on BFA-induced apoptosis. Furthermore, Jurkat cells transfected with the proto-oncoprotein Bcl-2, which is able to block various apoptotic conditions, showed remarkable resistance to the apoptotic effect of BFA. Thus, the data indicate that BFA- induced apoptosis requires caspase(s) activation, primarily the activation of caspase-3, and is inhibited by overexpression of Bcl-2.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalExperimental Cell Research
Issue number1
StatePublished - Nov 25 1998

ASJC Scopus subject areas

  • Cell Biology


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