Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor

  • Authors:
    • Dom‑Gene Tu
    • Yun Yu
    • Che‑Hsin Lee
    • Yu‑Liang Kuo
    • Yin‑Che Lu
    • Chi‑Wen Tu
    • Wen‑Wei Chang
  • View Affiliations

  • Published online on: March 2, 2016     https://doi.org/10.3892/ol.2016.4300
  • Pages: 2934-2940
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Abstract

Hinokitiol, alternatively known as β‑thujaplicin, is a tropolone‑associated natural compound with antimicrobial, anti‑inflammatory and antitumor activity. Breast cancer stem/progenitor cells (BCSCs) are a subpopulation of breast cancer cells associated with tumor initiation, chemoresistance and metastatic behavior, and may be enriched by mammosphere cultivation. Previous studies have demonstrated that BCSCs exhibit vasculogenic mimicry (VM) activity via the epidermal growth factor receptor (EGFR) signaling pathway. The present study investigated the anti‑VM activity of hinokitiol in BCSCs. At a concentration below the half maximal inhibitory concentration, hinokitiol inhibited VM formation of mammosphere cells derived from two human breast cancer cell lines. Hinokitiol was additionally indicated to downregulate EGFR protein expression in mammosphere‑forming BCSCs without affecting the expression of messenger RNA. The protein stability of EGFR in BCSCs was also decreased by hinokitiol. The EGFR protein expression and VM formation capability of hinokitiol‑treated BCSCs were restored by co‑treatment with MG132, a proteasome inhibitor. In conclusion, the present study indicated that hinokitiol may inhibit the VM activity of BCSCs through stimulating proteasome‑mediated EGFR degradation. Hinokitiol may act as an anti‑VM agent, and may be useful for the development of novel breast cancer therapeutic agents.
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April-2016
Volume 11 Issue 4

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

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Spandidos Publications style
Tu DG, Yu Y, Lee CH, Kuo YL, Lu YC, Tu CW and Chang WW: Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor. Oncol Lett 11: 2934-2940, 2016
APA
Tu, D., Yu, Y., Lee, C., Kuo, Y., Lu, Y., Tu, C., & Chang, W. (2016). Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor. Oncology Letters, 11, 2934-2940. https://doi.org/10.3892/ol.2016.4300
MLA
Tu, D., Yu, Y., Lee, C., Kuo, Y., Lu, Y., Tu, C., Chang, W."Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor". Oncology Letters 11.4 (2016): 2934-2940.
Chicago
Tu, D., Yu, Y., Lee, C., Kuo, Y., Lu, Y., Tu, C., Chang, W."Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor". Oncology Letters 11, no. 4 (2016): 2934-2940. https://doi.org/10.3892/ol.2016.4300