Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47phox pathway

Tsai, Ming-Horng; Lin, Zih-Chan; Liang, Cher‐Wei; Yen, Feng‐Lin; Chiang, Yu-Ting; Lee, Chiang‐Wen

doi:10.1016/j.taap.2014.06.012

Cited by 35 publications

(30 citation statements)

References 38 publications

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“…These data indicated that Nox2-mediated ROS generation may participate in artocarpin-induced oxidative damage to DNA and apoptosis in A549 and H1299 cells. Furthermore, previous studies have shown that during the process of Nox2 activation, the p47 phox cytosolic subunit is phosphorylated and translocates with the p67 phox subunit to the cell membrane, and combine with the gp91 phox (Nox2) subunit to form an active enzyme complex [33]. Therefore, we found that artocarpin induced phosphorylation of p47 phox in a time dependent manner (Figure 2G), and promoted p47 phox translocation from the cytoplasm to the cell membrane in 30 min.…”

Section: Resultsmentioning

confidence: 99%

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Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells

Tsai

Liu²,

Chiang

et al. 2017

Oncotarget

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Artocarpin has been shown to exhibit cytotoxic effects on different cancer cells, including non-small cell lung carcinoma (NSCLC, A549). However, the underlying mechanisms remain unclear. Here, we explore both p53-dependent and independent apoptosis pathways in artocarpin-treated NSCLC cells. Our results showed that artocarpin rapidly induced activation of cellular protein kinases including Erk1/2, p38 and AktS473. Inhibition of these protein kinases prevented artocarpin-induced cell death. Moreover, artocarpin-induced phosphorylation of these protein kinases and apoptosis were mediated by induction of reactive oxygen species (ROS), as pretreatment with NAC (a ROS scavenger) and Apocynin (a Nox-2 inhibitor) blocked these events. Similarly, transient transfection of p47Phox or p91Phox siRNA attenuated artocarpin-induced NADPH oxidase activity and cell death. In addition, p53 dependent apoptotic proteins including PUMA, cytochrome c, Apaf-1 and caspase 3 were activated by artocarpin, and these effects can be abolished by antioxidants, MAPK inhibitors (U0126 and SB202190), but not by PI3K inhibitor (LY294002). Furthermore, we found that artocarpin-induced Akt phosphorylation led to increased NF-κB activity, which may act as an upstream regulator in the c-Myc and Noxa pathway. Therefore, we propose that enhancement of both ERK/ p38/ p53-dependent or independent AktS473/NF-κB/c-Myc/Noxa cascade by Nox-derived ROS generation plays an important role in artocarpin-induced apoptosis in NSCLC cells.

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Section: Resultsmentioning

confidence: 99%

“…The cytosolic and plasma membrane fractions were isolated as previously described [33]. Cells were lysed in lysis buffer, and then centrifuged at 16,000 g for 20 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells

Tsai

Liu²,

Chiang

et al. 2017

Oncotarget

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“…cDNA obtained from 0.5 μg total RNA was used as a template for PCR amplification, as previously described22. The reverse transcriptase reaction was carried out using Moloney murine leukemia virus reverse transcriptase (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

Lee

Lin

et al. 2016

Sci Rep

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152

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We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.

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“…Consequently, their roles in tightly regulated redox signaling pathways are areas of intense study [25, 26]. The activation of NADPH oxidase is initiated by translocation of Rac1, p67phox, and p47phox from cytoplasm to the membrane [13, 27]. In an HL-60 cell line, Park and his co-workers found that CK2 can phosphorylate p47phox, as well as CK2 inhibition by DRB can facilitate translocation of p47phox [28].…”

Section: Discussionmentioning

confidence: 99%

5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury

et al. 2016

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5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2α and 2α' protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2α and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2α and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke.

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Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47phox pathway

Cited by 35 publications

References 38 publications

Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells

Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells

Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury

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