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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 1,267 - 1,279 (13page)
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Background Reactive oxygen species (ROS) generation specifically in cancer cells may be a promising strategy for theirselective killing. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one(DPP23) exerts antitumor activity through ROS-mediated apoptosis in cancer cells but not in healthy cells. However, themechanism underlying ROS generation by DPP23 remains unknown. Objective The current study aims to identify possible DPP23 target genes responsible for ROS generation through the miningof microarray data stored in NCBI’s Gene Expression Omnibus (GEO). Methods A comprehensive expression profile of genes modulated by DPP23 was examined by gene ontology analysis. DPP23-modulated genes in Mia-PaCa2 pancreatic cells were validated by reverse transcription-PCR. Results Multiple genes were up and downregulated by DPP23 treatment in MiaPaCa2 pancreatic cancer cells. Genes withabsolute fold-change (FC) of > 2 were selected as the cut-off criteria and grouped into 10 clusters to analyze expression patternssystematically. We observed that genes with increased expression at 6 h were significantly affected by ROS increase,unfolded protein response, and cell death. Expression of 13 genes involved in glutathione metabolism, including CHAC1,GCLC, G6PD, GSTO2, GSTA5, GSTM2, GSR, GPX3/6/8, GGT1, PGD, ATF4, and NAT8B, are modulated by DPP23. Ofthese, CHAC1 was most highly upregulated upon DPP23 treatment. Conclusion DPP23 alters global gene expression associated with multiple cellular responses, including oxidative stress andapoptosis. We found that DPP23 may induce GSH depletion through modulation of gene expression, which is especiallyinvolved in glutathione metabolism. Of these, CHAC1 emerged as the most prominent candidate for DPP23 as it was themost responsive to DPP23 treatment.
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참고문헌 (38)
참고문헌 신청
Adams DJ / 2012 / Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs / Proc Natl Acad Sci USA 109:15115~15120
Armstrong JS / 2002 / Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line / Cell Death Differ 9:252~263
Bachhawat AK / 2017 / Glutathione degradation / Antioxid Redox Signal 27:1200~1216
Boonstra J / 2004 / Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells / Gene 337:1~13
Cairns RA / 2011 / Regulation of cancer cell metabolism / Nat Rev Cancer 11:85~95
Armstrong JS / 2002 / Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line / Cell Death Differ 9:252~263
Bachhawat AK / 2017 / Glutathione degradation / Antioxid Redox Signal 27:1200~1216
Boonstra J / 2004 / Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells / Gene 337:1~13
Cairns RA / 2011 / Regulation of cancer cell metabolism / Nat Rev Cancer 11:85~95
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