Inhibition of tumor necrosis factor-α enhances apoptosis induced by nuclear factor-κB inhibition in leukemia cells

Abstract

Abstract. Inhibition of nuclear factor-κB (NF-κB) results in antitumor activity in leukemia cells, and may be a potential therapeutic strategy for the treatment of leukemia. However, a significant limitation of NF-κB inhibition in the treatment of leukemia is the low efficiency of this technique. NF-κB inhibitor treatment induces apoptosis in leukemia cells; however, it additionally causes inflammatory molecules to induce increased sensitivity of healthy hematopoietic cells to cell death signals, therefore limiting its clinical applications. Tumor necrosis factor-α (TNF-α) is a key regulator of inflammation, and induces a variety of actions in leukemic and healthy hematopoietic cells. TNF-α induces NF-κB-dependent and -independent survival signals, promoting the proliferation of leukemia cells. However, in healthy hematopoietic cells, TNF-α induces death signaling, an effect which is enhanced by the inhibition of NF-κB. Based on these observations, the present study hypothesized that inhibition of TNF-α signaling may be able to protect healthy hematopoietic cells and other tissue cells, while increasing the anti-leukemia effects of NF-κB inhibition on leukemia cells. The role and underlying molecular mechanisms of TNF-α inhibition in the regulation of NF-κB inhibition-induced apoptosis in leukemia cells was therefore investigated in the present study. The results indicated that inhibition of TNF-α enhanced NF-κB inhibition-induced apoptosis in leukemia cells. It was also revealed that protein kinase B was significant in the regulation of TNF-α and NF-κB inhibition-induced apoptosis. During this process, intrinsic apoptotic pathways were activated. A combination of NF-κB and TNF-α inhibition may be a potential specific and effective novel therapeutic strategy for the treatment of leukemia.

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

“…TNF-α upregulates expression of matrix degrading matrix metalloproteinases (MMPs 2 ) and two major aggrecanases (ADAMTS-4 and ADAMTS-5) by NPCs [16–18]. PI3K and its target PKB/Akt have emerged as critical signaling molecules that regulate multiple cellular processes, including survival and proliferation in numerous systems [19–21]. Matthew et al [22] demonstrated that PI3K and Akt could suppress TNF-induced apoptosis in MCF-7cells, while simultaneously increasing NF-κB activity.…”

El caseinato de sodio y la caseína α inhiben la proliferación de la línea celular mieloide de ratón 32D clone 3 (32Dcl3) mediante el TNF-α

“…Nuestros datos revelan que ni las caseínas ni el caseinato de sodio alteran la viabilidad celular detectada mediante el MTT, una prueba que evidencia la actividad metabólica mitocondrial (que solo tiene lugar en células vivas) (24), lo cual no coincide con la ligera inducción de translocación de fosfatidilserina causada por todas las caseínas, especialmente, por el caseinato de sodio (23 %) y la caseína α (16 %), justamente en las condiciones en que se observa la liberación de TNF-α, un promotor de la inducción de la apoptosis (25). La translocación de fosfatidilserina a la cara externa de la membrana es un evento temprano de inducción de la apoptosis y, por lo tanto, es reversible (26).…”

Melilotus indicus extract induces apoptosis in hepatocellular carcinoma cells via a mechanism involving mitochondria-mediated pathways

“…Furthermore, Karakaş et al (2012) showed that Melilotus officinalis and Melilotus alba extracts have great tumor inhibition activities. From a mechanistic point of view, however the anti-inflammatory effect of Melilotus extract could be attributed to the inhibition of TNF-a mRNA, COX-2 mRNA, and NF-kB (Zhang et al 2007), such candidates are implicated in the apoptotic pathways in cancer cells (Dong et al 2015), the underlying anticancer mechanisms of Melilotus extracts have remained completely unknown. Therefore, we aimed through studying the effect of M. indicus extract on cell proliferation of human hepatocellular carcinoma cell lines to elucidate its anticancer mechanism.…”