4-Hydroxypanduratin A and Isopanduratin A Inhibit Tumor Necrosis Factor α-Stimulated Gene Expression and the Nuclear Factor κB-Dependent Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

Abstract

Tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine, regulates inflammatory and immune responses by up-regulating gene expression in a manner that is dependent on the transcription factor nuclear factor κB (NF-κB). In the present study, we found that 4-hydroxypanduratin A and isopanduratin A, constituents of the rhizomes of Boesenbergia pandurata, inhibited the TNF-α-stimulated up-regulation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells. 4-Hydroxypanduratin A and isopanduratin A also reduced ICAM-1 mRNA expression and NF-κB-responsive luciferase activity in TNF-α-stimulated A549 cells. Moreover, 4-hydroxypanduratin A and isopanduratin A prevented the TNF-αstimulated translocation of the NF-κB subunit p65 to the nucleus and the phosphorylation and proteasomal degradation of the inhibitor of the NF-κB α protein. The present results revealed that 4-hydroxypanduratin A and isopanduratin A inhibit TNF-α-stimulated gene expression and the NF-κB-dependent signaling pathway in A549 cells.

Isopanduratin A Inhibits Tumor Necrosis Factor (TNF)-α-Induced Nuclear Factor κB Signaling Pathway by Promoting Extracellular Signal-Regulated Kinase-Dependent Ectodomain Shedding of TNF Receptor 1 in Human Lung Adenocarcinoma A549 Cells

“…To clarify whether isopanduratin A inhibits the converged NF-κB signaling pathway, A549 cells were pretreated with isopanduratin A, followed by TNF-α or IL-1α. Consistent with our previous findings [34], isopanduratin A inhibited IκBα degradation induced by TNF-α (Figure 1B). By contrast, IκBα degradation induced by IL-1α was not inhibited by isopanduratin A (Figure 1B).…”

“…Consistent with our previous findings [34], isopanduratin A inhibited the nuclear translocation of RelA in A549 cells stimulated with TNF-α (Figure 5A, Lanes 3 and 4). The pretreatment with TAPI-2 markedly suppressed the isopanduratin A-induced inhibition of the nuclear translocation of RelA (Figure 5A, Lanes 4 and 6).…”

“…Consistent with previous findings [32], we showed that isopanduratin A exhibited anti-cancer activity towards PANC-1 and the human hepatocellular carcinoma cell line HepG2 [31,33]. In addition to these anti-cancer activities, we recently reported that isopanduratin A inhibited the TNF-α-induced NF-κBdependent signaling pathway in the human lung adenocarcinoma cell line A549 [34]. 4-Hydroxypanduratin A has also been shown to inhibit the TNF-α-induced NF-κB-dependent signaling pathway [34].…”

“…In addition to these anti-cancer activities, we recently reported that isopanduratin A inhibited the TNF-α-induced NF-κBdependent signaling pathway in the human lung adenocarcinoma cell line A549 [34]. 4-Hydroxypanduratin A has also been shown to inhibit the TNF-α-induced NF-κB-dependent signaling pathway [34]. Consistent with our studies, panduratin A and its derivatives inhibited the NF-κB signaling pathway in different cell lines [35][36][37][38].…”

Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

“…The translocation of the NF-κB subunit RelA from the cytoplasm to the nucleus was observed in A549 cells within 30 min of the TNF-α stimulation [28,31]. The TNF-α stimulation induced an approximately 2-fold increase in nuclear RelA levels (Figure 6B-D).…”