scholarly journals Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3517-3525 ◽  
Author(s):  
Manoj K. Pandey ◽  
Bokyung Sung ◽  
Kwang Seok Ahn ◽  
Ajaikumar B. Kunnumakkara ◽  
Madan M. Chaturvedi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transferrin Receptor ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Chemotherapeutic Agents ◽  
Gambogic Acid ◽  
Human Leukemia ◽  
Gene Products ◽  
Signaling Mechanism

Abstract Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-κB signaling pathway, we investigated the effects of GA on NF-κB–mediated cellular responses and NF-κB–regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-xL, and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-κB. GA suppressed NF-κB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IκBα phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-κB–dependent reporter gene expression. The NF-κB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKβ was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-κB and apoptosis. Overall our results demonstrate that GA inhibits NF-κB signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor.

scholarly journals Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-κB–regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-κBα kinase, leading to potentiation of apoptosis

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 4880-4891 ◽  
Author(s):  
Bokyung Sung ◽  
Manoj K. Pandey ◽  
Kwang Seok Ahn ◽  
Tingfang Yi ◽  
Madan M. Chaturvedi ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Chemotherapeutic Agents ◽  
Anacardic Acid ◽  
Nuclear Factor ◽  
Gene Products ◽  
Down Regulation

Abstract Anacardic acid (6-pentadecylsalicylic acid) is derived from traditional medicinal plants, such as cashew nuts, and has been linked to anticancer, anti-inflammatory, and radiosensitization activities through a mechanism that is not yet fully understood. Because of the role of nuclear factor-κB (NF-κB) activation in these cellular responses, we postulated that anacardic acid might interfere with this pathway. We found that this salicylic acid potentiated the apoptosis induced by cytokine and chemotherapeutic agents, which correlated with the down-regulation of various gene products that mediate proliferation (cyclin D1 and cyclooxygenase-2), survival (Bcl-2, Bcl-xL, cFLIP, cIAP-1, and survivin), invasion (matrix metalloproteinase-9 and intercellular adhesion molecule-1), and angiogenesis (vascular endothelial growth factor), all known to be regulated by the NF-κB. We found that anacardic acid inhibited both inducible and constitutive NF-κB activation; suppressed the activation of IκBα kinase that led to abrogation of phosphorylation and degradation of IκBα; inhibited acetylation and nuclear translocation of p65; and suppressed NF-κB–dependent reporter gene expression. Down-regulation of the p300 histone acetyltransferase gene by RNA interference abrogated the effect of anacardic acid on NF-κB suppression, suggesting the critical role of this enzyme. Overall, our results demonstrate a novel role for anacardic acid in potentially preventing or treating cancer through modulation of NF-κB signaling pathway.

The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells

2014 ◽  
Vol 306 (12) ◽  
pp. C1119-C1128 ◽  
Author(s):  
Xiao-Juan Feng ◽  
Shu-Xia Liu ◽  
Chao Wu ◽  
Peng-Peng Kang ◽  
Qing-Juan Liu ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
High Mobility ◽  
Nuclear Factor Κb ◽  
Pyrrolidine Dithiocarbamate ◽  
Chromosomal Protein ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-κB signaling pathway.

scholarly journals Heat shock protein 90–mediated inactivation of nuclear factor-κB switches autophagy to apoptosis through becn1 transcriptional inhibition in selenite-induced NB4 cells

2011 ◽  
Vol 22 (8) ◽  
pp. 1167-1180 ◽  
Author(s):  
Qian Jiang ◽  
Yuhan Wang ◽  
Tianjiao Li ◽  
Kejian Shi ◽  
Zhushi Li ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Nuclear Translocation ◽  
Leukemia Cell ◽  
Heat Shock Protein 90 ◽  
Nuclear Factor Κb ◽  
Regulatory Function ◽  
Human Leukemia ◽  
Nuclear Factor ◽  
Nb4 Cells

Autophagy can protect cells while also contributing to cell damage, but the precise interplay between apoptosis and autophagy and the contribution of autophagy to cell death are still not clear. Previous studies have shown that supranutritional doses of sodium selenite promote apoptosis in human leukemia NB4 cells. Here, we report that selenite treatment triggers opposite patterns of autophagy in the NB4, HL60, and Jurkat leukemia cell lines during apoptosis and provide evidence that the suppressive effect of selenite on autophagy in NB4 cells is due to the decreased expression of the chaperone protein Hsp90 (heat shock protein 90), suggesting a novel regulatory function of Hsp90 in apoptosis and autophagy. Excessive or insufficient expression indicates that Hsp90 protects NB4 cells from selenite-induced apoptosis, and selenite-induced decreases in the expression of Hsp90, especially in NB4 cells, inhibit the activities of the IκB kinase/nuclear factor-κB (IKK/NF-κB) signaling pathway, leading to less nuclear translocation and inactivation of NF-κB and the subsequent weak binding of the becn1 promoter, which facilitates the transition from autophagy to apoptosis. Taken together, our observations provide novel insights into the mechanisms underlying the balance between apoptosis and autophagy, and we also identified Hsp90–NF-κB–Beclin1 as a potential biological pathway for signaling the switch from autophagy to apoptosis in selenite-treated NB4 cells.

Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-κB–regulated gene products and TAK1-mediated NF-κB activation

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2727-2735 ◽  
Author(s):  
Gautam Sethi ◽  
Kwang Seok Ahn ◽  
Manoj K. Pandey ◽  
Bharat B. Aggarwal
Keyword(s):  
Proinflammatory Cytokine ◽  
Nuclear Translocation ◽  
Cellular Responses ◽  
Chemotherapeutic Agents ◽  
Quinone Methide ◽  
Gene Products ◽  
Tripterygium Wilfordii ◽  
Cox 2 ◽  
Induced Apoptosis ◽  
Iκbα Degradation

Abstract Celastrol, a quinone methide triterpene derived from the medicinal plant Tripterygium wilfordii, has been used to treat chronic inflammatory and autoimmune diseases, but its mechanism is not well understood. Therefore, we investigated the effects of celastrol on cellular responses activated by TNF, a potent proinflammatory cytokine. Celastrol potentiated the apoptosis induced by TNF and chemotherapeutic agents and inhibited invasion, both regulated by NF-κB activation. We found that TNF induced the expression of gene products involved in antiapoptosis (IAP1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin), proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression. Because these gene products are regulated by NF-κB, we postulated that celastrol mediates its effects by modulating the NF-κB pathway. We found that celastrol suppressed both inducible and constitutive NF-κB activation. Celastrol was found to inhibit the TNF-induced activation of IκBα kinase, IκBα phosphorylation, IκBα degradation, p65 nuclear translocation and phosphorylation, and NF-κB–mediated reporter gene expression. Recent studies indicate that TNF-induced IKK activation requires activation of TAK1, and we indeed found that celastrol inhibited the TAK1-induced NF-κB activation. Overall, our results suggest that celastrol potentiates TNF-induced apoptosis and inhibits invasion through suppression of the NF-κB pathway.

scholarly journals Murine Coronavirus Induces Type I Interferon in Oligodendrocytes through Recognition by RIG-I and MDA5

2010 ◽  
Vol 84 (13) ◽  
pp. 6472-6482 ◽  
Author(s):  
Jianfeng Li ◽  
Yin Liu ◽  
Xuming Zhang
Keyword(s):  
Nuclear Translocation ◽  
Type I Interferon ◽  
Hepatitis Virus ◽  
Uv Light ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Type I ◽  
Small Interfering Rnas ◽  
Murine Coronavirus

ABSTRACT The murine coronavirus mouse hepatitis virus (MHV) induced the expression of type I interferon (alpha/beta interferon [IFN-α/β]) in mouse oligodendrocytic N20.1 cells. This induction is completely dependent on virus replication, since infection with UV light-inactivated virus could no longer induce IFN-α/β. We show that MHV infection activated both transcription factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor κB (NF-κB), as evidenced by phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF-3 and NF-κB. Furthermore, the cytoplasmic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) was induced by MHV infection. Knockdown of RIG-I by small interfering RNAs blocked the activation of IRF-3 and subsequent IFN-α/β production induced by MHV infection. Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-β induction. These results demonstrate that MHV is recognized by both RIG-I and MDA5 and induces IFN-α/β through the activation of the IRF-3 signaling pathway. However, knockdown of RIG-I only partially blocked NF-κB activity induced by MHV infection and inhibition of NF-κB activity by a decoy peptide inhibitor had little effect on IFN-α/β production. These data suggest that activation of the NF-κB pathway might not play a critical role in IFN-α/β induction by MHV infection in oligodendrocytes.

Ameliorative Effect of Rhoifolin in Cisplatin-Induced Nephrotoxicity via Regulating Nuclear Factor-κB Pathway

2020 ◽  
Vol 18 (3) ◽  
pp. 266-272
Author(s):  
Song Yanfang ◽  
Yan Shufang ◽  
Zhang Hong ◽  
Liu Rui ◽  
An Xin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Renal Damage ◽  
Nuclear Translocation ◽  
Intraperitoneal Administration ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ameliorative Effect ◽  
Factor Α

Dose-dependent nephrotoxicity limits the therapeutic use of cisplatin in tumor chemotherapy. Natural compounds show a protective effect against cisplatin-induced nephrotoxicity. Rhoifolin is a flavone glycoside that demonstrates antioxidant and antiproliferative effects. The influence and mechanism of rhoifolin on cisplatin-induced nephrotoxicity were investigated in this study. First, a rat model of cisplatin-induced nephrotoxicity was established. Intraperitoneal administration of cisplatin induced renal damage in rats as demonstrated by a decrease in body weight, increase in blood urea, nitrogen and creatinine, and destruction of histological integrity. However, treatment with rhoifolin attenuated cisplatin-induced nephrotoxicity. Second, cisplatin induced oxidative stress and inflammatory response in rats as demonstrated by a decrease in superoxide dismutase, glutathione, glutathione S-transferase and catalase, and an increase in malondialdehyde, tumor necrosis factor-α, and interleukin-6. Also, the administration of rhoifolin led to alleviation of cisplatin-induced oxidative stress and inflammatory response. Finally, cisplatin activated the nuclear factor-kappa B signaling pathway via degradation and phosphorylation of IκBα (inhibitor of kappa B). Administration of rhoifolin inhibited nuclear translocation of NF-κB via down-regulation of phospho-IκBα and phospho-p65, as well as up-regulation of IκBα. In conclusion, the administration of rhoifolin attenuated cisplatin-induced renal damage, oxidative stress and inflammatory response through inhibition of the NF-κB signaling pathway, suggesting a potential adjunct candidate for cisplatin in tumor treatment.

Sign in / Sign up

Export Citation Format

Share Document