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Supplementary Figures 1 - 8 from NQO1 Suppresses NF-κB–p300 Interaction to Regulate Inflammatory Mediators Associated with Prostate Tumorigenesis

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posted on 2023-03-30, 22:51 authored by Dinesh Thapa, Peng Meng, Roble G. Bedolla, Robert L. Reddick, Addanki P. Kumar, Rita Ghosh

(S1) Basal NQO1 levels in different cancer cells, (S2) Transduction efficiency of NQO1 KD, (S3 and S4) Effects of KD on cellular redox state and AR signaling, (S5) heat maps of differential gene expression with NQO1 KD, (S6) inhibition of NQO1 activity on NFkB-p65 signaling, (S7) Quantification of increased nuclear IKKa following NQO1 KD and (S8) Basal IL-8 message in prostate cancer cells.

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ARTICLE ABSTRACT

NADPH reductase NAD(P)H:quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKKα and NF-κB while decreasing the levels of p53, leading to interactions between NF-κB and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune-associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-κB and p53 function. Cancer Res; 74(19); 5644–55. ©2014 AACR.

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