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Depletion of BIS sensitizes A549 cells to treatment with cisplatin

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Abstract

Bcl-2 interacting cell death suppressor (BIS), an anti-stress and ant-apoptotic protein, has been reported to be expressed at high levels in various cancers. In a previous study, we reported on a high level of expression of BIS in non small cell lung cancer tissues. To explore the significance this finding in lung cancer, in this study, we investigated the effect of BIS depletion on the survival of A549 cells upon treatment with anti-tumor agents. BIS knock out A549 cells, prepared by the CRISPR/Cas9 system, revealed a substantial decrease in survival to cisplatin treatment. Western blotting and quantitative real time PCR assays indicated that, among the anti-apoptotic Bcl-2 family proteins, the expression of Mcl-1 was decreased by BIS depletion at the protein level not at the mRNA level. Since BIS expression has been shown to be regulated by HSF1, we subsequently illustrated the sensitization effect of KRIBB11, a HSF1 inhibitor, on cisplatin-induced toxicity in A549 cells, accompanied by a decrease in both BIS and Mcl-1 expression. Our results suggest that BIS-mediated Mcl-1 stabilization represents a potential therapeutic target for cancer therapy.

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Authors and Affiliations

  1. Department of Biochemistry, The Catholic University of Korea, Seoul, 06591, Korea

    Mei Nu Cui, Hye-Hyeon Yun, Hye Yun Kim, Chang-Nim Im & Jeong-Hwa Lee

  2. The Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, 06591, Korea

    Mei Nu Cui, Hye-Hyeon Yun, Hye Yun Kim, Chang-Nim Im & Jeong-Hwa Lee

  3. Aging Intervention Research Center, KRIBB, Daejeon, 34141, Korea

    Nan Ee Lee & Yong-Sam Kim

  4. Korea University of Science and Technology, Daejeon, 34113, Korea

    Yong-Sam Kim

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  1. Mei Nu Cui
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Correspondence to Jeong-Hwa Lee.

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Cui, M.N., Yun, HH., Lee, N.E. et al. Depletion of BIS sensitizes A549 cells to treatment with cisplatin. Mol. Cell. Toxicol. 12, 63–71 (2016). https://doi.org/10.1007/s13273-016-0009-y

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  • DOI: https://doi.org/10.1007/s13273-016-0009-y

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