• Title/Summary/Keyword: m-ALDH

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Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

  • Jung, Yuchae;Park, Heejoo;Zhao, Hui-Yuan;Jeon, Raok;Ryu, Jae-Ha;Kim, Woo-Young
    • Molecules and Cells
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    • v.37 no.7
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    • pp.547-553
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    • 2014
  • Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

Eliminatory Effect of Health Drink Containing Hovenia Dulcis Thunb Extract on Ethanol-Induced Hangover in Rats (헛개나무 열매 추출물을 함유한 건강음료의 숙취 제거 효과)

  • Park, Eun-Mi;Ye, Eun-Ju;Kim, Soo-Jung;Choi, Hyun-Im;Bae, Man-Jong
    • Journal of the Korean Society of Food Culture
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    • v.21 no.1
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    • pp.71-75
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    • 2006
  • This study was conducted to investigate the eliminatory effect of health drink containing Hovenia dulcis Thunb extract on ethanol-induced hangover in rats. Male Sprague-Dawley rats weighing $200{\pm}10\;g$ were given health drink (10 mL/kg) or other company product(10 mL/kg) 30 min before or after 40% ethanol (5 g/kg body weight) ingestion. To study the effect of health drink on blood ethanol concentration, blood was taken from caudal artery at 1, 3, 5 hr and the animal were sacrificed 24 hr after ethanol ingestion. From 1 to 5 hr, health drink pre- or postdosing significantly decreased the ethanol levels in the blood. The acetaldehyde concentration showed decrement in health drink group and other company product group. The activities of ethanol, alcohol dehydrogenase and aldehyde dehydrogenase measured at postdosing, were also not altered by the administration of health drink. Alanine aminotransferase and aspartate aminotransferase activities showed unaltered resulted in all experimental groups compared with the normal group. These results suggest that oral intake of health drink containing Hovenia dulcis Thunb is effective on elimination of ethanol-induced hangover.