אסיף מאגר המחקר החקלאי

Strigolactone analogues induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells

Year:

2014

Source of publication :

Authors :

Volume :

5

Co-Authors:

Pollock, C.B., Department of Human Science, Georgetown University Medical Center, NW Washington, DC, United States, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States
McDonough, S., Department of Human Science, Georgetown University Medical Center, NW Washington, DC, United States
Wang, V.S., Department of Human Science, Georgetown University Medical Center, NW Washington, DC, United States
Lee, H., Department of Human Science, Georgetown University Medical Center, NW Washington, DC, United States
Ringer, L., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States, Department of Pathology, Georgetown University Medical Center, NW Washington, DC, United States, Center for Cellular Reprogramming, Georgetown University Medical Center, NW Washington, DC, United States
Li, X., Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, NW Washington, DC, United States
Prandi, C., Department of Chemistry, University Turin, Torino, Italy
Lee, R.J., Massachusetts General Hospital, Boston, MA, United States
Feldman, A.S., Massachusetts General Hospital, Boston, MA, United States
Koltai, H., Department of Ornamental Horticulture, Agricultural Research Organization (ARO), Bet Dagan, Israel
Kapulnik, Y., Department of Field Crops, Natural Resources Institute of Plant Sciences, Agricultural Research Organization (ARO), Bet Dagan, Israel
Rodriguez, O.C., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States, Department of Pathology, Georgetown University Medical Center, NW Washington, DC, United States, Center for Cellular Reprogramming, Georgetown University Medical Center, NW Washington, DC, United States
Schlegel, R., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States, Department of Pathology, Georgetown University Medical Center, NW Washington, DC, United States, Center for Cellular Reprogramming, Georgetown University Medical Center, NW Washington, DC, United States
Albanese, C., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States, Department of Pathology, Georgetown University Medical Center, NW Washington, DC, United States, Center for Cellular Reprogramming, Georgetown University Medical Center, NW Washington, DC, United States
Yarden, R.I., Department of Human Science, Georgetown University Medical Center, NW Washington, DC, United States, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW Washington, DC, United States

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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.

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