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

  • Published online on: February 21, 2018     https://doi.org/10.3892/ol.2018.8091
  • Pages: 6443-6449
  • Copyright: © Fujii et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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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