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Toxins 2016, 8(5), 127;

Ovatodiolide Inhibits Breast Cancer Stem/Progenitor Cells through SMURF2-Mediated Downregulation of Hsp27

Department of Anesthesiology, Changhua Christian Hospital, Changhua 500, Taiwan
Division of Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 402, Taiwan
School of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan
Institute of Microbiology & Immunology, Chung Shan Medical University, Taichung 40201, Taiwan
Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei 11221, Taiwan
Center for General Education, National Taitung University, Taitung 95092, Taiwan
Department of Appiled Chemistry, Chaoyang University of Technology, Taichung 41349, Taiwan
Authors to whom correspondence should be addressed.
Academic Editor: Carmela Fimognari
Received: 8 March 2016 / Revised: 12 April 2016 / Accepted: 20 April 2016 / Published: 28 April 2016
(This article belongs to the Special Issue Dietary and Non-Dietary Phytochemicals and Cancer)
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Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells involved in tumor initiation, resistance to therapy and metastasis. Targeting CSCs has been considered as the key for successful cancer therapy. Ovatodiolide (Ova) is a macrocyclic diterpenoid compound isolated from Anisomeles indica (L.) Kuntze with anti-cancer activity. Here we used two human breast cancer cell lines (AS-B145 and BT-474) to examine the effect of Ova on breast CSCs. We first discovered that Ova displayed an anti-proliferation activity in these two breast cancer cells. Ova also inhibited the self-renewal capability of breast CSCs (BCSCs) which was determined by mammosphere assay. Ova dose-dependently downregulated the expression of stemness genes, octamer-binding transcription factor 4 (Oct4) and Nanog, as well as heat shock protein 27 (Hsp27), but upregulated SMAD ubiquitin regulatory factor 2 (SMURF2) in mammosphere cells derived from AS-B145 or BT-474. Overexpression of Hsp27 or knockdown of SMURF2 in AS-B145 cells diminished the therapeutic effect of ovatodiolide in the suppression of mammosphere formation. In summary, our data reveal that Ova displays an anti-CSC activity through SMURF2-mediated downregulation of Hsp27. Ova could be further developed as an anti-CSC agent in the treatment of breast cancer. View Full-Text
Keywords: ovatodiolide; cancer stem/progenitor cells; Hsp27; SMURF2 ovatodiolide; cancer stem/progenitor cells; Hsp27; SMURF2

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Lu, K.-T.; Wang, B.-Y.; Chi, W.-Y.; Chang-Chien, J.; Yang, J.-J.; Lee, H.-T.; Tzeng, Y.-M.; Chang, W.-W. Ovatodiolide Inhibits Breast Cancer Stem/Progenitor Cells through SMURF2-Mediated Downregulation of Hsp27. Toxins 2016, 8, 127.

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