Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB

Life Sciences
Claudia MatteucciBeatrice Macchi

Abstract

The present study addresses the issue of enhanced apoptotic response to AZT following co-treatment with an NF-kB inhibitor. To investigate this issue, different cell lines were assayed for susceptibility to AZT-mediated apoptosis without or with the addition of the NF-kB inhibitor Bay-11-7085. For further investigation, U937 cells were selected as good-responder cells to the combination treatment with 32 or 128 μM AZT, and 1 μM Bay-11-7085. Inhibition of NF-kB activation by Bay-11-7085 in cells treated with AZT was assayed through Western blot analysis of p65 expression and by EMSA. Involvement of the mitochondrial pathway of apoptosis in mechanisms underlying the improved effect of AZT following Bay-11-7085 co-treatment, was evaluated by assaying the cytochrome c release and the mitochondrial membrane potential (MMP) status using the JC-1 dye. Moreover, the transcriptional activity of both anti- and pro-apoptotic genes in U937 cells after combination treatment was quantitatively evaluated through real-time PCR. We found that the combined treatment induced high levels of cytochrome c release and of MMP collapse in association with evident changes in the expression of both anti- and pro-apoptotic genes of the Bcl-2 family. Overe...Continue Reading

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Citations

Nov 7, 2019·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Alessandro GiovinazzoClaudia Matteucci
May 7, 2020·Pathogens·Francesca Marino-MerloBeatrice Macchi
Aug 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aisha S AhmedEva Kosek
May 22, 2018·Frontiers in Pharmacology·Ian F Caplan, Kathleen A Maguire-Zeiss
Aug 3, 2020·Developmental and Comparative Immunology·Jia-Yang HeHong-Yan Sun

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