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E-GEOD-54820 - Strigolactone analogs induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells

Status
Released on 10 February 2014, last updated on 3 June 2014
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (6)
Description
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. Furthermore, we tested the response of patient-matched conditionally reprogrammed normal and prostate cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis compared to their normal counterpart cells. Treatment of cancer cells with strigolactone analogues was hallmarked by increased expression and activity of genes involved in stress signaling, cell cycle arrest and apoptosis. All five strigolactone analogues induced G2/M cell cycle arrest, accompanied with a decrease in the expression level of cyclin B1. Apoptosis was marked by increased percentages of cells in the sub-G1 fraction and was confirmed by Annexin V staining. In conditionally reprogramed matched tumor and normal prostate cells, the cleavage of PARP1 confirmed the specific increase in apoptosis of tumor cells. In summary, 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. There are duplicate samples for each condition. U2OS cells were treated with 2 different strigolactone analogues: ST362 or MEB55 at the concentration of 5 ppm for either 6 hr or 24 hr.Control samples were those treated with vehicle only .
Experiment type
transcription profiling by array 
Contacts
Ronit Iris Yarden <riy2@georgetown.edu>, Adam S Feldman, Christopher Albanese, Claire B Pollock, Cristina Prandi, Hinanit Koltai, Hyojung C Lee, Lymor Ringer, Olga Rudrigaz, R J Lee, Richard Schlegel, Ronit I Yarden, Sara McDoungh, Victor S Wang, Yoram Kapulnik
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-54820.idf.txt
Sample and data relationshipE-GEOD-54820.sdrf.txt
Processed data (1)E-GEOD-54820.processed.1.zip
Additional data (1)E-GEOD-54820.additional.1.zip
Array designA-GEOD-10558.adf.txt
Links