Abstract
Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Treatment of cancer cells with strigolactone analogues was hallmarked by activation of the stress-related MAPKs: p38 and JNK and induction of stress-related genes; cell cycle arrest and apoptosis evident by increased percentages of cells in the sub-G1 fraction and Annexin V staining. In addition, we tested the response of patient-matched conditionally reprogrammed primary prostate normal and cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis confirmed by PARP1 cleavage compared to their normal counterpart cells. Thus, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Apoptosis / drug effects*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Blotting, Western
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Cell Cycle / drug effects
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Cell Cycle Checkpoints / drug effects
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Cell Proliferation / drug effects
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Gene Expression Profiling
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Lactones / pharmacology*
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Male
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Neoplasms / pathology*
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology*
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Oligonucleotide Array Sequence Analysis
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Prostate / drug effects
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Prostate / metabolism
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Tumor Cells, Cultured
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Biomarkers, Tumor
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GR24 strigolactone
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Heterocyclic Compounds, 3-Ring
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Lactones
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RNA, Messenger
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strigol
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases