• Title/Summary/Keyword: YM155

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YM155 Induces Apoptosis through Downregulation of Anti-apoptotic Proteins in Head and Neck AMC-HN4 Cells (YM155 처리에 의한 두경부 암 AMC-HN4 세포 세포자멸사 유도 효과)

  • Chang, Ho Joon;Kwon, Taeg Kyu;Kim, Dong Eun
    • Journal of Life Science
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    • v.29 no.3
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    • pp.318-324
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    • 2019
  • Squamous cell carcinoma is the primary tumor type in head and neck cancers, the fifth most common malignant neoplasm world-wide. Survivin, a member of the inhibitor of apoptosis family, is highly expressed in head and neck carcinoma patients and correlated with more aggressive forms. In this study, we investigated whether YM155, a specific survivin inhibitor, could induce apoptosis in head and neck AMC-HN4 cells. YM155 was found to markedly induce apoptosis and cleavage of PARP, a marker of apoptosis. Furthermore, YM155 promoted apoptosis in other cancer cells, such as glioma (U251MG) and renal carcinoma (Caki) cells. In contrast, YM155 had no effect on apoptosis in normal mesangial cells. YM155 significantly induced caspase activation, and pan caspase inhibitor z-VAD-fmk markedly blocked apoptosis, PARP cleavage, and caspase-3 cleavage. Therefore, YM155 was seen to instigate caspase-dependent apoptosis in head and neck AMC-HN4 cells, inducing downregulation of survivin as well as other apoptotic proteins such as c-FLIP and Mcl-1. In addition, the induction of apoptosis and PARP cleavage by YM155 treatment was effectively inhibited in survivin-, c-FLIP- and Mcl-1-over-expressing head and neck AMC-HN4 cells. In conclusion, YM155 is a potent candidate for inducing cell death in head and neck AMC-HN4 cells.

Biomedical Application of Gene Editing (유전자 교정 기술의 생의학적 응용)

  • Ju-Chan, Park;Hyeon-Ki, Jang
    • Journal of Industrial Technology
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    • v.42 no.1
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    • pp.29-36
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    • 2022
  • The CRISPR system has revolutionized gene editing field. Cas9-mediated gene editing such as Indel induction or HDR enable targeted gene disruption or precise correction of mutation. Moreover, CRISPR-based new editing tools have been developed such as base editors. In this review, we focus on gene editing in human pluripotent stem cells, which is principal technique for gene correction therapy and disease modeling. Pluripotent stem cell-specific drug YM155 enabled selection of target gene-edited pluripotent stem cells. Also, we discussed base editing for treatment of congenital retina disease. Adenine base editor delivery as RNP form provide an approach for genetic disease treatment with safe and precise in vivo gene correction.