Selective ROS-dependent p53-associated anticancer effects of the hypoxoside derivative rooperol on human teratocarcinomal cancer stem-like cells

详细信息    查看全文

• 作者：Sarah Ali Azouaou ; Fathi Emhemmed ; Noureddine Idris-Khodja…
• 关键词：Cancer stem ; like cells ; Rooperol ; Apoptosis ; Reactive oxygen species ; p53 ; Oct4
• 刊名：Investigational New Drugs
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：33
• 期：1
• 页码：64-74
• 全文大小：1,896 KB
• 参考文献：1. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51:1-8 CrossRef
  2. Sharif T, Emhemmed F, Fuhrmann G (2011) Towards new anticancer strategies by targeting cancer stem cells with phytochemical compounds. In: Shostak S (ed) Cancer Stem Cells - The Cutting Edge. Rijeka, Croatia, Intech, pp 431-56
  3. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645-48 CrossRef
  4. Visvader JE (2011) Cells of origin in cancer. Nature 469:314-22 CrossRef
  5. Surh YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3:768-80 CrossRef
  6. Chabner BA, Roberts TG Jr (2005) Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer 5:65-2 CrossRef
  7. Shu L, Cheung KL, Khor TO, Chen C, Kong AN (2010) Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis. Cancer Metastasis Rev 29:483-02 CrossRef
  8. Sharif T, Auger C, Bronner C, Alhosin M, Klein T, Etienne-Selloum N, Schini-Kerth VB, Fuhrmann G (2011) Selective proapoptotic activity of polyphenols from red wine on teratocarcinoma cell, a model of cancer stem-like cell. Invest New Drugs 29:239-47 CrossRef
  9. Sharif T, Stambouli M, Burrus B, Emhemmed F, Dandache I, Auger C, Etienne-Selloum N, Schini-Kerth VB, Fuhrmann G (2013) The polyphenolic-rich / Aronia melanocarpa juice kills teratocarcinomal cancer stem-like cells, but not their differentiated counterparts. J Funct Foods 5:1244-252 CrossRef
  10. Emhemmed F, Ali Azouaou S, Thuaud F, Schini-Kerth V, Désaubry L, Muller CD, Fuhrmann G (2014) Selective anticancer effects of a synthetic flavagline on human Oct4-expressing cancer stem-like cells via a p38 MAPK-dependent caspase-3-dependent pathway. Biochem Pharmacol 89:185-96 CrossRef
  11. Guzdek A, Turyna B, Allison AC, Sladek K, Koj A (1997) Rooperol, an inhibitor of cytokine synthesis, decreases the respiratory burst in human and rat leukocytes and macrophages. Mediators Inflamm 6:53-7 CrossRef
  12. Boukes GJ, van de Venter M (2012) Rooperol as an antioxidant and its role in the innate immune system: an in vitro study. J Ethnopharmacol 144:692-99 CrossRef
  13. Boukes GJ, Daniels BB, Albrecht CF, van de Venter M (2010) Cell survival or apoptosis: rooperol’s role as anticancer agent. Oncol Res 18:365-76 CrossRef
  14. Pesce M, Sch?ler HR (2001) Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19:271-78 CrossRef
  15. Jung M, Peterson H, Chavez L, Kahlem P, Lehrach H, Vilo J, Adjaye J (2010) A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells. PLoS One 5:e10709 CrossRef
  16. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947-56 CrossRef
  17. Kang J, Shakya A, Tantin D (
• 作者单位：Sarah Ali Azouaou (1) (2)
  Fathi Emhemmed (1) (2)
  Noureddine Idris-Khodja (1) (3)
  Annelise Lobstein (2)
  Valérie Schini-Kerth (1)
  Christian D. Muller (2)
  Guy Fuhrmann (1)
  
  1. UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401, Illkirch, France
  2. UMR 7200 CNRS, Laboratoire d’Innovation Thérapeutique, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401, Illkirch, France
  3. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 C?te-Ste-Catherine Rd., Montreal, QC, H3T 1E2, Canada
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

Cancer stem cells (CSCs) are potential targets for innovative anticancer therapies that involve natural products with potential chemopreventive effects. We therefore analyzed the antineoplastic activity of rooperol, the aglycone of the plant-derived compound hypoxoside, on a model of Oct4-expressing cancer stem-like cell, i.e. the human embryonal carcinoma (EC) cell NT2/D1. Rooperol selectively inhibited the proliferation of NT2/D1 cells in a concentration-dependent manner and had no effect on either normal embryonic fibroblasts which are more restrictive pluripotent stem cells or on NCCIT p53-mutant EC cells. Accordingly, rooperol only eliminates colon carcinoma cells expressing p53. Rooperol treatment triggered cell death on NT2/D1 cells through the alteration of mitochondrial membrane potential and production of reactive oxygen species (ROS). Rooperol-induced apoptosis was associated with activation of p53 and concentration-dependent changes of the expression levels of both caspase 3 and poly ADP ribose polymerase type 1 cleaved subunits. These modifications were accompanied by a downregulation of Oct4 and its two partners involved in the maintenance of cell pluripotency and self-renewal, Nanog and Sox2. Treatment with intracellular membrane permeant O2 ?/sup> scavengers prevented rooperol-induced apoptosis and upregulation of the expression of p53 and active caspase-3. Our findings indicate that rooperol mediates its growth inhibitory effects on CSCs via a mitochondrial redox-sensitive mechanism. We propose that abrogating the expression of the stemness regulators is a prerequisite for rooperol to fully exert its pro-apoptotic properties on wild-type p53-bearing CSCs.