Abstract
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.
Highlights
Cancer stem/progenitor cells (CSCs) have been described for decades and these particular cancer cells have been reported to be involved in tumor initiation, resistance to chemotherapy or radiotherapy, and metastasis [1,2]
Ginestier et al later reported that breast cancer cells with high intracellular aldehyde dehydrogenase (ALDH) activity represented the population of breast CSCs (BCSCs) [4]
We previously discovered that heat shock protein 27 (Hsp27) was upregulated in ALDH+ BCSCs [14]
Summary
Cancer stem/progenitor cells (CSCs) have been described for decades and these particular cancer cells have been reported to be involved in tumor initiation, resistance to chemotherapy or radiotherapy, and metastasis [1,2]. Breast CSCs were first identified by Al-Hajj et al with the marker of CD24-CD44+ [3]. Ginestier et al later reported that breast cancer cells with high intracellular aldehyde dehydrogenase (ALDH) activity represented the population of BCSCs [4]. Toxins 2016, 8, 127 surface markers or intracellular enzyme activity, BCSCs could be enriched with a cultivation method of the mammosphere, a clump of cancer cells with stem/progenitor cell properties [5]. Targeting CSCs is considered as a key for successful treatment in cancer [2,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
