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Article

Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells

  • Authors:
    • Jing Zhang
    • Osamu Yamada
    • Shinya Kida
    • Yoshihisa Matsushita
    • Shinya Murase
    • Toshio Hattori
    • Yuzuru Kubohara
    • Haruhisa Kikuchi
    • Yoshiteru Oshima
  • View Affiliations / Copyright

    Affiliations: Research and Development Center, FUSO Pharmaceutical Industries, Ltd., Osaka 536‑8523, Japan, Department of Disaster‑related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Miyagi 980‑8575, Japan, Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba 270‑1695, Japan, Laboratory of Natural Product Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980‑8578, Japan
  • Pages: 2357-2364
    |
    Published online on: August 5, 2016
       https://doi.org/10.3892/or.2016.5006
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Abstract

The contribution of aberrant osteopontin (OPN) expression to tumor progression and metastasis has been documented in a wide spectrum of malignancies, and targeted inhibition of OPN has therefore emerged as an attractive strategy for cancer therapy. Transcription of OPN is regulated by various transcription factors, and our recently published study demonstrated that downregulation of OPN is an important event in the TGF‑β cytostatic program. We report here that brefelamide exerts an inhibitory effect on OPN expression and function in A549 human lung carcinoma cells. The promoter, RNA, and protein levels of OPN were decreased in brefelamide‑treated A549 cells, which was accompanied by reduced invasive ability in vitro. OPN inhibition by brefelamide was largely abrogated by disruption of a putative TGF‑β inhibitory element in the OPN promoter. Treatment with brefelamide induced Smad4 expression, and knockdown of Smad4 by RNA interference partially diminished the inhibitory effect of brefelamide on OPN. These results indicate that brefelamide inhibited OPN‑mediated cell invasion through restoration of the OPN repression by TGF‑β/Smad signaling. Together with the reported antiproliferative property, our findings suggest that brefelamide might serve as a potential candidate for the development of a new antitumor and antimetastatic agent.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Yamada O, Kida S, Matsushita Y, Murase S, Hattori T, Kubohara Y, Kikuchi H and Oshima Y: Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncol Rep 36: 2357-2364, 2016.
APA
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T. ... Oshima, Y. (2016). Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncology Reports, 36, 2357-2364. https://doi.org/10.3892/or.2016.5006
MLA
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T., Kubohara, Y., Kikuchi, H., Oshima, Y."Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells". Oncology Reports 36.4 (2016): 2357-2364.
Chicago
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T., Kubohara, Y., Kikuchi, H., Oshima, Y."Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells". Oncology Reports 36, no. 4 (2016): 2357-2364. https://doi.org/10.3892/or.2016.5006
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Yamada O, Kida S, Matsushita Y, Murase S, Hattori T, Kubohara Y, Kikuchi H and Oshima Y: Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncol Rep 36: 2357-2364, 2016.
APA
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T. ... Oshima, Y. (2016). Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncology Reports, 36, 2357-2364. https://doi.org/10.3892/or.2016.5006
MLA
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T., Kubohara, Y., Kikuchi, H., Oshima, Y."Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells". Oncology Reports 36.4 (2016): 2357-2364.
Chicago
Zhang, J., Yamada, O., Kida, S., Matsushita, Y., Murase, S., Hattori, T., Kubohara, Y., Kikuchi, H., Oshima, Y."Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells". Oncology Reports 36, no. 4 (2016): 2357-2364. https://doi.org/10.3892/or.2016.5006
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