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Figure 7 | Breast Cancer Research

Figure 7

From: Phospho-ibuprofen (MDC-917) suppresses breast cancer growth: an effect controlled by the thioredoxin system

Figure 7

Effect of phospho-ibuprofen against breast cancer: proposed mechanism of action. In this model, phospho-ibuprofen (P-I) suppresses breast cancer growth through its dual effect on: reactive oxygen and nitrogen species (RONS), inducing oxidative stress; and the thioredoxin (Trx) system, inhibiting the thioredoxin reductase (TrxR) activity, oxidizing thioredoxin-1 (Trx-1) and suppressing its expression. These effects lead to decreased cell proliferation and increased apoptosis, their net result suppressed breast cancer growth or even tumor regression. Specifically, P-I-induced RONS convert proteins from their reduced (Protein-red) to oxidized (Protein-ox) state. Trx-1, Trx-1-(SH)2, reduces its oxidized client proteins - itself, however, being oxidized in the process (Trx-1-S2). TrxR recycles Trx-1-S2 back to its normal reduced state. The shaded areas explain how the effect of P-I on redox signaling (NF-κB and apoptosis signal-regulating kinase 1 (ASK1)-p38/JNK) is controlled by the central Trx system.

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