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Article Open Access

Bufalin induces DNA damage response under hypoxic condition in myeloma cells

  • Authors:
    • Eri Fujii
    • Yuki Inada
    • Misaki Kakoki
    • Nao Nishimura
    • Shinya Endo
    • Shiho Fujiwara
    • Naoko Wada
    • Yawara Kawano
    • Yutaka Okuno
    • Toshiya Sugimoto
    • Hiroyuki Hata
  • View Affiliations / Copyright

    Affiliations: Graduate School of Health Sciences, Course of Medical Laboratory Sciences, Kumamoto University, Kumamoto 862‑0976, Japan, Department of Hematology, Faculty of Medical Sciences, Kumamoto University, Kumamoto 860‑8556, Japan
    Copyright: © Fujii et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6443-6449
    |
    Published online on: February 21, 2018
       https://doi.org/10.3892/ol.2018.8091
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Abstract

Hypoxia serves a crucial role in the development of drug resistance in various cancer cells. Therefore, many attempts targeting hypoxia are underway to overcome the drug resistance mediated by hypoxia. This strategy is useful for multiple myeloma (MM) cells, as MM cells reside within the bone marrow, where oxygen concentrations are relatively low. A natural compound library was screened to identify compounds exerting cytotoxicity in MM cells under hypoxic conditions. Bufalin exhibited marked cytotoxicity to MM cells under normoxic and hypoxic conditions. No significant toxicity was observed in lymphocytes obtained from healthy donors. Under normoxic conditions, bufalin induced a DNA double strand break (DSB) response, ROS induction and apoptosis within 24 with a rapid response compared with melphalan. Interestingly, the bufalin‑induced DSB response was not impaired by low oxygen concentrations while the DSB response by melphalan was reduced. Furthermore, treatment with bufalin abolished HIF‑1α expression under hypoxia, suggesting that bufalin exerts cytotoxicity under hypoxia by regulating HIF‑1α. These results indicate that bufalin induces apoptosis in MM cells through DSB under hypoxic conditions by inhibiting HIF‑1α, suggesting that bufalin could be useful for eradication of drug‑resistant MM cells in the hypoxic microenvironment.
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Copy and paste a formatted citation
Spandidos Publications style
Fujii E, Inada Y, Kakoki M, Nishimura N, Endo S, Fujiwara S, Wada N, Kawano Y, Okuno Y, Sugimoto T, Sugimoto T, et al: Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncol Lett 15: 6443-6449, 2018.
APA
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S. ... Hata, H. (2018). Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncology Letters, 15, 6443-6449. https://doi.org/10.3892/ol.2018.8091
MLA
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S., Wada, N., Kawano, Y., Okuno, Y., Sugimoto, T., Hata, H."Bufalin induces DNA damage response under hypoxic condition in myeloma cells". Oncology Letters 15.5 (2018): 6443-6449.
Chicago
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S., Wada, N., Kawano, Y., Okuno, Y., Sugimoto, T., Hata, H."Bufalin induces DNA damage response under hypoxic condition in myeloma cells". Oncology Letters 15, no. 5 (2018): 6443-6449. https://doi.org/10.3892/ol.2018.8091
Copy and paste a formatted citation
x
Spandidos Publications style
Fujii E, Inada Y, Kakoki M, Nishimura N, Endo S, Fujiwara S, Wada N, Kawano Y, Okuno Y, Sugimoto T, Sugimoto T, et al: Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncol Lett 15: 6443-6449, 2018.
APA
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S. ... Hata, H. (2018). Bufalin induces DNA damage response under hypoxic condition in myeloma cells. Oncology Letters, 15, 6443-6449. https://doi.org/10.3892/ol.2018.8091
MLA
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S., Wada, N., Kawano, Y., Okuno, Y., Sugimoto, T., Hata, H."Bufalin induces DNA damage response under hypoxic condition in myeloma cells". Oncology Letters 15.5 (2018): 6443-6449.
Chicago
Fujii, E., Inada, Y., Kakoki, M., Nishimura, N., Endo, S., Fujiwara, S., Wada, N., Kawano, Y., Okuno, Y., Sugimoto, T., Hata, H."Bufalin induces DNA damage response under hypoxic condition in myeloma cells". Oncology Letters 15, no. 5 (2018): 6443-6449. https://doi.org/10.3892/ol.2018.8091
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