Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome‑mediated degradation of epidermal growth factor receptor
- Dom‑Gene Tu
- Yun Yu
- Che‑Hsin Lee
- Yu‑Liang Kuo
- Yin‑Che Lu
- Chi‑Wen Tu
- Wen‑Wei Chang
Affiliations: Department of Nuclear Medicine, Ditmanson Medical Foundation Chia‑Yi Christian Hospital, Chiayi 60002, Taiwan, R.O.C., School of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C., Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C., Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C., Division of Hematology‑Oncology, Ditmanson Medical Foundation Chia‑Yi Christian Hospital, Chiayi 60002, Taiwan, R.O.C., Department of Surgery, Ditmanson Medical Foundation Chia‑Yi Christian Hospital, Chiayi 60002, Taiwan, R.O.C.
- Published online on: March 2, 2016 https://doi.org/10.3892/ol.2016.4300
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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.