6-Dehydrogingerdione sensitizes human hepatoblastoma hep G2 cells to trail-induced apoptosis via reactive oxygen species-mediated increase of dr5

Chung Yi Chen, Cheng Jeng Tai, Jiin Tsuey Cheng, Juan Juan Zheng, Ying Zong Chen, Tsan Zon Liu, Shuenn Jiun Yiin, Chi Liang Chern

研究成果: 雜誌貢獻文章

21 引文 (Scopus)

摘要

The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale, and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial-and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial-and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.

原文英語
頁(從 - 到)5604-5611
頁數8
期刊Journal of Agricultural and Food Chemistry
58
發行號9
DOIs
出版狀態已發佈 - 五月 12 2010

指紋

Hepatoblastoma
Hep G2 Cells
reactive oxygen species
Reactive Oxygen Species
apoptosis
Apoptosis
cells
CD95 Antigens
Zingiber officinale
receptors
Acetylcysteine
rendering
Ginger
small interfering RNA
6-dehydrogingerdione
Phosphorylation
Rhizome
Madin Darby Canine Kidney Cells
rhizomes
cysteine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

引用此文

6-Dehydrogingerdione sensitizes human hepatoblastoma hep G2 cells to trail-induced apoptosis via reactive oxygen species-mediated increase of dr5. / Chen, Chung Yi; Tai, Cheng Jeng; Cheng, Jiin Tsuey; Zheng, Juan Juan; Chen, Ying Zong; Liu, Tsan Zon; Yiin, Shuenn Jiun; Chern, Chi Liang.

於: Journal of Agricultural and Food Chemistry, 卷 58, 編號 9, 12.05.2010, p. 5604-5611.

研究成果: 雜誌貢獻文章

Chen, Chung Yi ; Tai, Cheng Jeng ; Cheng, Jiin Tsuey ; Zheng, Juan Juan ; Chen, Ying Zong ; Liu, Tsan Zon ; Yiin, Shuenn Jiun ; Chern, Chi Liang. / 6-Dehydrogingerdione sensitizes human hepatoblastoma hep G2 cells to trail-induced apoptosis via reactive oxygen species-mediated increase of dr5. 於: Journal of Agricultural and Food Chemistry. 2010 ; 卷 58, 編號 9. 頁 5604-5611.
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abstract = "The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale, and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial-and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial-and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.",
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AU - Chen, Chung Yi

AU - Tai, Cheng Jeng

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AU - Zheng, Juan Juan

AU - Chen, Ying Zong

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AU - Yiin, Shuenn Jiun

AU - Chern, Chi Liang

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N2 - The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale, and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial-and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial-and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.

AB - The anticancer effects of 6-dehydrogingerdione (6-DG), a compound isolated from the rhizomes of Zingiber officinale, and its mechanisms of sensitization to TRAIL-induced apoptosis were studied using human hepatoblastoma Hep G2 cells. This study demonstrates for the first time that 6-DG-induced apoptosis might be executed via mitochondrial-and Fas receptor-mediated pathways. Further studies also demonstrated that 6-DG could sensitize Hep G2 cells to TRAIL-induced apoptosis. 6-DG also up-regulated Ser-15 phosphorylation and evoked p53 nuclear translocation. Abrogation of p53 expression by p53 small interfering RNA significantly attenuated 6-DG-induced DR5 expression, thus rendering these cells resistant to TRAIL-induced apoptosis. DR5 expression after 6-DG treatment was accompanied by provoking intracellular reactive oxygen species (ROS) generation. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated 6-DG-induced DR5 expression and inhibited TRAIL-induced apoptosis. In contrast to Hep G2 cells, DR5 up-regulation and sensitization to TRAIL-induced apoptosis instigated by 6-DG were not observed in normal MDCK cells. Taken together, these data suggested that in addition to the mitochondrial-and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.

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