• Title/Summary/Keyword: $p21^{WAF1/CIP1}$

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Induction of Apoptosis by Methanol Extract of Endlicheria anomala in Human Lung and Liver Cancer Cells (Endlicheria anomala 메탄올 추출물에 의한 인체 폐암세포주와 간암세포주의 자가사멸 유도)

  • Park, Hyun-jin;Jin, Soojung;Oh, You Na;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.25 no.4
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    • pp.441-449
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    • 2015
  • Endlicheria anomala, a neotropical plant, is found in northern South America and the Amazon region. It is traditionally used to remove poisons and cure gangrene. According to recent data, this plant has diverse biological properties such as anti-oxidative, anti-inflammatory and anti-melanogenic properties. However, the anti-cancer effect of E. anomala and its molecular mechanisms remain unclear. In this study, we examined the anti-cancer effect and the active mechanism of methanol extract of E. anomala (MEEA) in human lung adenocarcinoma cells (A549) and human liver cancer cells (HepG2). Our data revealed that MEEA showed cytotoxic activity in a dose-dependent manner and induced apoptosis both in A549 and HepG2 cells. We verified evidences of apoptosis via formation of chromatin condensation, apoptotic body and accumulation of cells in the subG1 phase. Following observed apoptosis-related phenomena, we found that the induction of apoptosis by MEEA was associated with the increase of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. Furthermore, MEEA-induced apoptosis was characterized with proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of pro-apoptotic Bax expression. Taken together, these findings indicate that MEEA may have potential cancer therapeutic utility in A549 and HepG2 cells.

Shallow subsurface structure of the Vulcano-Lipari volcanic complex, Italy, constrained by helicopter-borne aeromagnetic surveys (고해상도 항공자력탐사를 이용한 Italia Vulcano-Lipari 화산 복합체의 천부 지하 구조)

  • Okuma, Shigeo;Nakatsuka, Tadashi;Komazawa, Masao;Sugihara, Mitsuhiko;Nakano, Shun;Furukawa, Ryuta;Supper, Robert
    • Geophysics and Geophysical Exploration
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    • v.9 no.1
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    • pp.129-138
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    • 2006
  • Helicopter-borne aeromagnetic surveys at two different times separated by three years were conducted to better understand the shallow subsurface structure of the Vulcano and Lipari volcanic complex, Aeolian Islands, southern Italy, and also to monitor the volcanic activity of the area. As there was no meaningful difference between the two magnetic datasets to imply an apparent change of the volcanic activity, the datasets were merged to produce an aeromagnetic map with wider coverage than was given by a single dataset. Apparent magnetisation intensity mapping was applied to terrain-corrected magnetic anomalies, and showed local magnetisation highs in and around Fossa Cone, suggesting heterogeneity of the cone. Magnetic modelling was conducted for three of those magnetisation highs. Each model implied the presence of concealed volcanic products overlain by pyroclastic rocks from the Fossa crater. The model for the Fossa crater area suggests a buried trachytic lava flow on the southern edge of the present crater. The magnetic model at Forgia Vecchia suggests that phreatic cones can be interpreted as resulting from a concealed eruptive centre, with thick latitic lavas that fill up Fossa Caldera. However, the distribution of lavas seems to be limited to a smaller area than was expected from drilling results. This can be explained partly by alteration of the lavas by intense hydrothermal activity, as seen at geothermal areas close to Porto Levante. The magnetic model at the north-eastern Fossa Cone implies that thick lavas accumulated as another eruption centre in the early stage of the activity of Fossa. Recent geoelectric surveys showed high-resistivity zones in the areas of the last two magnetic models.

Fisetin Protects C2C12 Mouse Myoblasts from Oxidative Stress-Induced Cytotoxicity through Regulation of the Nrf2/HO-1 Signaling

  • Cheol Park;Hee-Jae Cha;Da Hye Kim;Chan-Young Kwon;Shin-Hyung Park;Su Hyun Hong;EunJin Bang;Jaehun Cheong;Gi-Young Kim;Yung Hyun Choi
    • Journal of Microbiology and Biotechnology
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    • v.33 no.5
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    • pp.591-599
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    • 2023
  • Fisetin is a bioactive flavonol molecule and has been shown to have antioxidant potential, but its efficacy has not been fully validated. The aim of the present study was to investigate the protective efficacy of fisetin on C2C12 murine myoblastjdusts under hydrogen peroxide (H2O2)-induced oxidative damage. The results revealed that fisetin significantly weakened H2O2-induced cell viability inhibition and DNA damage while blocking reactive oxygen species (ROS) generation. Fisetin also significantly alleviated cell cycle arrest by H2O2 treatment through by reversing the upregulation of p21WAF1/CIP1 expression and the downregulation of cyclin A and B levels. In addition, fisetin significantly blocked apoptosis induced by H2O2 through increasing the Bcl-2/Bax ratio and attenuating mitochondrial damage, which was accompanied by inactivation of caspase-3 and suppression of poly(ADP-ribose) polymerase cleavage. Furthermore, fisetin-induced nuclear translocation and phosphorylation of Nrf2 were related to the increased expression and activation of heme oxygenase-1 (HO-1) in H2O2-stimulated C2C12 myoblasts. However, the protective efficacy of fisetin on H2O2-mediated cytotoxicity, including cell cycle arrest, apoptosis and mitochondrial dysfunction, were greatly offset when HO-1 activity was artificially inhibited. Therefore, our results indicate that fisetin as an Nrf2 activator effectively abrogated oxidative stress-mediated damage in C2C12 myoblasts.

Clostridium difficile Toxin A Inhibits Wnt Signaling Pathway in Gut Epithelial Cells (대장상피세포 속 Wnt 신호 경로에 대한 C. difficile 톡신A의 영향)

  • Yoon, I Na;Kim, Ho
    • Journal of Life Science
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    • v.28 no.9
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    • pp.1016-1021
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    • 2018
  • Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; $p21^{CIP1/WAF1}$ upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced ${\beta}$-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced ${\beta}$-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of ${\beta}$-catenin, indicating that toxin A may activate intracellular processes, such as $GSK3{\beta}$, to promote degradation of ${\beta}$-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of $GSK3{\beta}$. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.

Induction of G2/M Arrest and Apoptosis by the Methanol Extract of Typha orientalis in Human Colon Adenocarcinoma HT29 Cells (포황 메탄올 추출물에 의한 인체 대장암 세포주 HT29의 G2/M Arrest 및 Apoptosis 유발)

  • Jin, Soojung;Yun, Seung-Geun;Oh, You Na;Lee, Ji-Young;Park, Hyun-Jin;Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.41 no.4
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    • pp.425-432
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    • 2013
  • Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.