Strigolactones: a novel class of phytohormones that inhibit the growth and survival of breast cancer cells and breast cancer stem-like enriched mammosphere cells
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Several naturally occurring phytohormones have shown enormous potential in the prevention and treatment of variety of different type of cancers. Strigolactones (SLs) are a novel class of plant hormones produced in roots and regulate new above ground shoot branching, by inhibiting self-renewal of undifferentiated meristem cells. Here, we study the effects of six synthetic SL analogs on breast cancer cell lines growth and survival. We show that SL analogs are able to inhibit proliferation and induce apoptosis of breast cancer cells but to a much lesser extent “non-cancer” lines. Given the therapeutic problem of cancer recurrence which is hypothesized to be due to drug resistant cancer stem cells, we also tested the ability of SL analogs to inhibit the growth of mammosphere cultures that are typically enriched with cancer stem-like cells. We show that SLs are potent inhibitors of self-renewal and survival of breast cancer cell lines grown as mammospheres and even a short exposure leads to irreversible effects on mammosphere dissociation and cell death. Immunoblot analysis revealed that SLs analogs induce activation of the stress response mediated by both P38 and JNK1/2 MAPK modules and inhibits PI3K/AKT activation. Taken together this study indicates that SLs may be promising anticancer agents whose activities may be achieved through modulation of stress and survival signaling pathways.
KeywordsPlant hormone Strigolactone GR24 Breast cancer Apoptosis Proliferation Mammosphere Cancer stem cell p38 MAPK JNK1/2
Cancer stem cell
Parts per million
Extracellular signal-regulated kinase
- p38 MAPK
p38 mitogen-activated protein kinase
Mitogen- and stress-activated protein kinase
Activating transcription factor 2
Protein kinase B
We gratefully thank Drs. Rebecca Riggins, York Tomita, and Michael Johnson (Lombardi Cancer Centre) for sharing reagents and helpful discussion. We thank the flow cytometry core facility at Lombardi Cancer Center for assistance with the cell cycle analysis. This study was supported by the Department of Defense Breast Program W81XWH-11-1-0190 (RIY) and by the BioBits Project, Regione Piemonte, Italy (CP).
Conflict of interest
The authors declare that there is no conflict of interests.
- 15.Kapulnik Y, Delaux PM, Resnick N, Mayzlish-Gati E, Wininger S, Bhattacharya C, Sejalon-Delmas N, Combier JP, Becard G, Belausov E, Beeckman T, Dor E, Hershenhorn J, Koltai H (2011) Strigolactones affect lateral root formation and root-hair elongation in Arabidopsis. Planta 233:209–216PubMedCrossRefGoogle Scholar
- 20.Koltai H, Dor E, Hershenhorn J, Daniel M, Weininger S, Lekalla S, Shealtiel H, Bhattacharya C, Eliahu E, Resnick N, Barg R, Kapulnik Y (2010) Strigolactones’ effect on root growth and root-hair elongation may be mediated by auxin-efflux carriers. J Plant Growth Regul 29:129–136CrossRefGoogle Scholar
- 27.Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, Brown M, Viens P, Xerri L, Bertucci F, Stassi G, Dontu G, Birnbaum D, Wicha MS (2009) Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 69:1302–1313PubMedCrossRefGoogle Scholar