Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways

Mitsuho Imai-Sumida, Takeshi Chiyomaru, Shahana Majid, Sharanjot Saini, Hannah Nip, Rajvir Dahiya, Yuichiro Tanaka, Soichiro Yamamura

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been studied extensively. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation, migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide 3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines. These pathways were found to crosstalk through RAS cascades. We found that silibinin suppressed levels of trimethylated histone H3 lysine 4 and acetylated H3 at the KRAS promoter. Furthermore, silibinin targets long non-coding RNA: HOTAIR and ZFAS1, which are known to play roles as oncogenic factors in various cancers. This study shows that silibinin exerts anti-cancer effects through down-regulation of actin cytoskeleton and PI3K/Akt pathways and thus suppresses bladder cancer growth and progression.

Original languageEnglish (US)
Pages (from-to)92032-92042
Number of pages11
JournalOncotarget
Volume8
Issue number54
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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Keywords

  • Bladder cancer
  • KRAS
  • Long non-coding RNA
  • PI3K
  • Silibinin

ASJC Scopus subject areas

  • Oncology

Cite this

Imai-Sumida, M., Chiyomaru, T., Majid, S., Saini, S., Nip, H., Dahiya, R., Tanaka, Y., & Yamamura, S. (2017). Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways. Oncotarget, 8(54), 92032-92042. https://doi.org/10.18632/oncotarget.20734