Co-Authors:
Pollock, C.B., Department of Human Science, Georgetown University, St. Mary's Hall, Washington, DC 20007, United States, Lombardi Comprehensive Cancer Center, Georgetown University, Medical Center, 3700 Reservoir Road, NW, Washington, DC 20057, United States
Koltai, H., Department of Ornamental Horticulture, Agricultural Research Organization (ARO), Volcani Center, PO Box 6, 50250 Bet Dagan, Israel
Kapulnik, Y., Department of Field Crops, Natural Resources Institute of Plant Sciences, Agricultural Research Organization (ARO), PO Box 6, 50250 Bet Dagan, Israel
Prandi, C., Department of Chemistry, University Turin, via P. Giuria 7, 10125 Turin, Italy
Yarden, R.I., Department of Human Science, Georgetown University, St. Mary's Hall, Washington, DC 20007, United States, Lombardi Comprehensive Cancer Center, Georgetown University, Medical Center, 3700 Reservoir Road, NW, Washington, DC 20057, United States
Abstract:
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 ishypothesized to bedueto 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. © Springer Science+Business Media, LLC. 2012.
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