Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors

Abstract

The current scientific literature has extensively explored the potential role of proteasome inhibitors (PIs) in the NF-κB pathway of leukemia and lymphoma. The ubiquitin-proteasome system (UPS) is a critical component in regulating protein degradation in eukaryotic cells. PIs, such as BTZ, are used to target the 26S proteasome in hematologic malignancies, resulting in the prevention of the degradation of tumor suppressor proteins, the activation of intrinsic mitochondrial-dependent cell death, and the inhibition of the NF-κB signaling pathway. NF-κB is a transcription factor that plays a critical role in the regulation of apoptosis, cell proliferation, differentiation, inflammation, angiogenesis, and tumor migration. Despite the successful use of PIs in various hematologic malignancies, there are limitations such as resistant to these inhibitors. Some reports suggest that PIs can induce NF-κB activation, which increases the survival of malignant cells. This article discusses the various aspects of PIs’ effects on the NF-κB pathway and their limitations.

The Potential Regenerative Effect of L-carnitine Pretreated Mesenchymal Stem Cells in Myocardial Infarction Through Modulating Apoptosis, Inflammation, and Cellular Differentiation

“…This impairment is associated with a significant inflammatory response revealed by injury of the endothelial cells with leukocyte infiltration and elevation of the inflammatory cytokines; IL-1 β, IL-6, and Tnf-α [72,73 and 65]. Consistent with the previous studies, the current work demonstrated the elevation of the inflammatory mediators; IL-1 β, Tnf-α, NF-ҡβ, and apoptotic factor; caspase 3 with a decrease of the antiapoptotic factor; Bcl2 in DOX-treated group as documented by Wang et al [48] and Pakjoo et al [74]. On the other hand, the L-carnitine-pretreated MSCs group showed the optimum results in decreasing the measured inflammatory, apoptotic, and fibrotic cytokines, and antiapoptotic Bcl2 elevation producing improvement of the structural architecture of cardiac muscles.…”