Strigolactones: a novel class of phytohormones that inhibit the growth and survival of breast cancer cells and breast cancer stem-like enriched mammosphere cells

• Published in: Breast cancer research and treatment 2012-08, Vol.134 (3), p.1041-1055
• Main Authors: Pollock, C. B., Koltai, H., Kapulnik, Y., Prandi, C., Yarden, R. I.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Breast cancer; Breast Neoplasms - metabolism; Cancer cells; Cancer research; Cancer therapies; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Female; Flowers & plants; Gibberellins; Growth; Gynecology. Andrology. Obstetrics; Health aspects; Hormones; Humans; Inhibitory Concentration 50; Lactones - pharmacology; Mammary gland diseases; MCF-7 Cells; Medical sciences; Medicine; Medicine & Public Health; Mitogen-Activated Protein Kinases - metabolism; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Oncology; Plant Growth Regulators - pharmacology; Preclinical Study; Signal Transduction - drug effects; Spheroids, Cellular; Stem cells; Stress, Physiological; Tumor Cells, Cultured; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-012-1992-x

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.