• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.447-448
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• 2008

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.503-509
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• 2014

Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.

• Natural Product Sciences
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• v.14 no.2
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• pp.81-85
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• 2008

Isorhamnetin isolated from Oenanthe javanica significantly inhibited proliferation and collagen production in HSC-T6 cells in concentration- and time-dependent manners. Pretreatment of HSC-T6 cells with isorhamnetin significantly inhibited serum-induced ERK phosphorylation, in a similar manner as PD98059, a known MEK inhibitor. These results suggested that isorhamnetin reduced collagen production in HSC-T6 cells, in part, via inhibition of ERK signaling pathway.

• Journal of Life Science
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• v.18 no.8
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• pp.1023-1030
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• 2008

NtMEK2, which is the tobacco MAPK kinase that is upstream of SIPK and WIPK, was identified using the dexamethasone (DEX)-inducible gain-of-function transgenic system. Expression of $NtNEK2^{DD}$, a constitutively active mutant of NtNEK2, leads to HR-like cell death, which indicates that the NtMEK2-SIPK/WIPK cascade controls defense responses in tobacco. However, little is known about the downstream target substrates or defense-related genes that are regulated by the NtMEK2-SIPK/ WIPK cascade. In this study, ACP-based differential display RT-PCR was used to isolate the downstream effectors mediated by the NtMEK2-SIPK/WIPK cascade in $NtNEK2^{DD}$ transgenic plants. The results identified 6 novel differentially expressed genes (DEGs). These included pathogen induced protein 2-4 (pI2-4), monoterpene synthase 2 (MTS2), seven in absentia protein (SINA), cell death marker protein 1 (CDM1), hydroxyproline-rich glycoprotein (HRGP) and unknown genes (DEG45). The induction of these genes was confirmed by RT-PCR of samples obtained from $NtNEK2^{DD}$ plants. Additionally, when compared with other isolated DEGs, the pI2-4, CDM1 and HRGP genes were significantly up-regulated in response to treatment with salicylic acid and tobacco mosaic virus. Taken together, these results suggest that three novel DEGs were regulated by the NtMEK2-SIPK/WIPK cascade involved in disease resistance in tobacco.

• Biomedical Science Letters
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• v.19 no.1
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• pp.1-8
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• 2013

Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.579-585
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• 2015

Rutin is a well-known flavonoid found in buckwheat. Recent studies have demonstrated that the biological actions of rutin include anti-inflammatory and anti-cancer effects, but the underlying molecular mechanisms of these actions are not yet fully understood. Neoplastic cell transformation is considered a major event that contributes to carcinogenesis, and the present study aimed to determine whether rutin would exert anti-tumor effects via the results suggest that rutin exerted a potent inhibitory influence on the molecular activity of the MEK/ERK and MKK4/JNK pathways and strongly attenuated EGF-induced neoplastic cell transformation. These findings provide insight into the biological actions of rutin and the molecular basis for the development of new chemoprotective agents.

• Journal of Microbiology and Biotechnology
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• v.19 no.11
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• pp.1355-1363
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• 2009

In the present study, the neuroprotective effects of astaxanthin on $H_2O_2$-mediated apoptotic cell death, using cultured mouse neural progenitor cells (mNPCs), were investigated. To cause apoptotic cell death, mNPCs were pretreated with astaxanthin for 8 h and followed by treatment of 0.3 mM $H_2O_2$. Pretreatment of mNPCs with astaxanthin significantly inhibited $H_2O_2$-mediated apoptosis and induced cell growth in a dose-dependent manner. In Western blot analysis, astaxanthin-pretreated cells showed the activation of p-Akt, p-MEK, p-ERK, and Bcl-2, and the reduction of p-P38, p-SAPK/JNK, Bax, p-GSK3b, cytochrome c, caspase-3, and PARP. Because $H_2O_2$ triggers caspases activation, this study examined whether astaxanthin can inhibit caspases activation in $H_2O_2$-treated mNPCs. After $H_2O_2$ treatment, caspases activities were prominently increased, but astaxanthin pretreatment significantly inhibited $H_2O_2$-mediated caspases activation. Astaxanthin pretreatment also significantly recovered the ATP production ability of $H_2O_2$-treated cells. These findings indicate that astaxanthin inhibits $H_2O_2$-mediated apoptotic features in mNPCs. Inhibition assays with SB203580 ($10\;{\mu}M$, a specific inhibitor of p38) and PD98059 ($10\;{\mu}M$, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit $H_2O_2$-mediated apoptotic death via modulation of p38 and MEK signaling pathways.

• BMB Reports
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• v.48 no.2
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.95.1-95.1
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• 2007

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• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.167-174
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• 2014

Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated the effects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models, and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation, survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasion and tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with $10{\mu}M$ barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vessel development more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H and E staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore, it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanoma cells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT, FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the MEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibit tumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling pathway. The findings support further investigation of barbigerone as a potential anti-cancer drug.